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Wang H, Baba Y, Hara Y, Toihata T, Kosumi K, Harada K, Iwatsuki M, Miyamoto Y, Baba H. The Relationship Between Gut Microbiome Bifidobacterium and Anti-tumor Immune Responses in Esophageal Squamous Cell Carcinoma. Ann Surg Oncol 2025; 32:3828-3838. [PMID: 40035906 PMCID: PMC11976794 DOI: 10.1245/s10434-024-16288-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2024] [Accepted: 09/17/2024] [Indexed: 03/06/2025]
Abstract
BACKGROUND The Bifidobacterium genus is a prominent bacterial population in the gastrointestinal tract. Previous findings suggest that Bifidobacterium is linked to tumor suppression in mouse models of melanoma. Additionally, when combined with the programmed death-ligand 1 (PD-L1) antibody, it can enhance anti-tumor treatment by increasing tumor-specific T-cell responses and promoting infiltration of antigen-specific T cells into tumors. However, there is a lack of studies on Bifidobacterium in esophageal squamous cell carcinoma (ESCC). This study aimed to investigate the potential impact of Bifidobacterium on this cancer type. METHODS We examined 213 samples from ESCC patients who underwent tumor resection. The presence of Bifidobacterium was confirmed using quantitative polymerase chain reaction and fluorescent in situ hybridization (FISH). Patient overall survival (OS) was analyzed with Bifidobacterium positivity. Tumor-infiltrating lymphocytes (TILs) were evaluated via hematoxylin and eosin stains, and immunohistochemistry was used to assess programmed death-1 (PD-1), PD-L1, cluster of differentiation 8 (CD8), and forkhead box P3 (FOXP3) expression. Nutritional status was evaluated via computed tomography scans. RESULTS Bifidobacterium positivity showed no correlation with patient OS or TIL levels; however, Bifidobacterium positivity in normal tissue was associated with lower FOXP3 levels, suggesting a potential role in upregulating anti-tumor immune responses. Patients with Bifidobacterium present in peritumor normal tissue exhibited better skeletal muscle area and volume. Conversely, Bifidobacterium positivity in tumor tissue was associated with poorer prognostic nutrition index values, likely due to decreased albumin levels. CONCLUSION Bifidobacterium can induce the upregulated anti-tumor immune response and is more prevalent in cases with good nutritional status.
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Affiliation(s)
- Haolin Wang
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Yoshifumi Baba
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
| | - Yoshihiro Hara
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Tasuku Toihata
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Keisuke Kosumi
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Kazuto Harada
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Masaaki Iwatsuki
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Yuji Miyamoto
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Hideo Baba
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
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2
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Zhang Q, Li M, Jin X, Zhou R, Ying Y, Wu X, Jing J, Pan W. Comparison of interventions for Barrett's esophagus: A network meta-analysis. PLoS One 2024; 19:e0302204. [PMID: 38709808 PMCID: PMC11073690 DOI: 10.1371/journal.pone.0302204] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2023] [Accepted: 03/30/2024] [Indexed: 05/08/2024] Open
Abstract
BACKGROUND AND OBJECTIVE Barrett's esophagus (BE) is a precancerous condition that has the potential to develop into esophageal cancer (EC). Currently, there is a wide range of management options available for individuals at different pathological stages in Barrett's esophagus (BE). However, there is currently a lack of knowledge regarding their comparative efficacy. To address this gap, we conducted a network meta-analysis of published randomized controlled trials to examine the comparative effectiveness of all regimens. METHODS Data extracted from eligible randomized controlled trials were utilized in a Bayesian network meta-analysis to examine the relative effectiveness of BE's treatment regimens and determine their ranking in terms of efficacy. The ranking probability for each regimen was assessed using the surfaces under cumulative ranking values. The outcomes under investigation were complete ablation of BE, neoplastic progression of BE, and complete eradication of dysplasia. RESULTS We identified twenty-three RCT studies with a total of 1675 participants, and ten different interventions. Regarding complete ablation of non-dysplastic BE, the comparative effectiveness ranking indicated that argon plasma coagulation (APC) was the most effective regimen, with the highest SUCRA value, while surveillance and PPI/H2RA were found to be the least efficacious regimens. For complete ablation of BE with low-grade dysplasia, high-grade dysplasia, or esophageal cancer, photodynamic therapy (PDT) had the highest SUCRA value of 94.1%, indicating it as the best regimen. Additionally, for complete eradication of dysplasia, SUCRA plots showed a trend in ranking PDT as the highest with a SUCRA value of 91.2%. Finally, for neoplastic progression, radiofrequency ablation (RFA) and surgery were found to perform significantly better than surveillance. The risk of bias assessment revealed that 6 studies had an overall high risk of bias. However, meta-regression with risk of bias as a covariate did not indicate any influence on the model. In terms of the Confidence in Network Meta-Analysis evaluation, a high level of confidence was found for all treatment comparisons. CONCLUSION Endoscopic surveillance alone or PPI/H2RA alone may not be sufficient for managing BE, even in cases of non-dysplastic BE. However, APC has shown excellent efficacy in treating non-dysplastic BE. For cases of BE with low-grade dysplasia, high-grade dysplasia, or esophageal cancer, PDT may be the optimal intervention as it can induce regression of BE metaplasia and prevent future progression of BE to dysplasia and EC.
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Affiliation(s)
- Qinlin Zhang
- Department of Gastroenterology, Sanmen County People’s Hospital, Taizhou, Zhejiang, China
- Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Miya Li
- Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Xin Jin
- Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Ruhong Zhou
- Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Yize Ying
- Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Xueping Wu
- Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Jiyong Jing
- Department of Gastroenterology, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Wensheng Pan
- Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
- Department of Gastroenterology, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, China
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3
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Park HC, Li D, Liang R, Adrales G, Li X. Multifunctional Ablative Gastrointestinal Imaging Capsule (MAGIC) for Esophagus Surveillance and Interventions. BME FRONTIERS 2024; 5:0041. [PMID: 38577399 PMCID: PMC10993155 DOI: 10.34133/bmef.0041] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2023] [Accepted: 03/04/2024] [Indexed: 04/06/2024] Open
Abstract
Objective and Impact Statement: A clinically viable technology for comprehensive esophagus surveillance and potential treatment is lacking. Here, we report a novel multifunctional ablative gastrointestinal imaging capsule (MAGIC) technology platform to address this clinical need. The MAGIC technology could also facilitate the clinical translation and adoption of the tethered capsule endomicroscopy (TCE) technology. Introduction: Recently developed optical coherence tomography (OCT) TCE technologies have shown a promising potential for surveillance of Barrett's esophagus and esophageal cancer in awake patients without the need for sedation. However, it remains challenging with the current TCE technology for detecting early lesions and clinical adoption due to its suboptimal resolution, imaging contrast, and lack of visual guidance during imaging. Methods: Our technology reported here integrates dual-wavelength OCT imaging (operating at 800 and 1300 nm), an ultracompact endoscope camera, and an ablation laser, aiming to enable comprehensive surveillance, guidance, and potential ablative treatment of the esophagus. Results: The MAGIC has been successfully developed with its multimodality imaging and ablation capabilities demonstrated by imaging swine esophagus ex vivo and in vivo. The 800-nm OCT imaging offers exceptional resolution and contrast for the superficial layers, well suited for detecting subtle changes associated with early neoplasia. The 1300-nm OCT imaging provides deeper penetration, essential for assessing lesion invasion. The built-in miniature camera affords a conventional endoscopic view for assisting capsule deployment and laser ablation. Conclusion: By offering complementary and clinically viable functions in a single device, the reported technology represents an effective solution for endoscopic screening, diagnosis, and potential ablation treatment of the esophagus of a patient in an office setting.
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Affiliation(s)
- Hyeon-Cheol Park
- Department of Biomedical Engineering,
Johns Hopkins University, Baltimore, MD 21205, USA
| | - Dawei Li
- Department of Biomedical Engineering,
Johns Hopkins University, Baltimore, MD 21205, USA
- Department of College of Future Technology,
Peking University, Beijing, 100871, China
| | - Rongguang Liang
- College of Optical Sciences,
University of Arizona, Tucson, AZ 85721, USA
| | - Gina Adrales
- Department of Surgery,
Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
| | - Xingde Li
- Department of Biomedical Engineering,
Johns Hopkins University, Baltimore, MD 21205, USA
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4
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Ebert MP, Fischbach W, Hollerbach S, Höppner J, Lorenz D, Stahl M, Stuschke M, Pech O, Vanhoefer U, Porschen R. S3-Leitlinie Diagnostik und Therapie der Plattenepithelkarzinome und Adenokarzinome des Ösophagus. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:535-642. [PMID: 38599580 DOI: 10.1055/a-2239-9802] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/12/2024]
Affiliation(s)
- Matthias P Ebert
- II. Medizinische Klinik, Medizinische Fakultät Mannheim, Universitätsmedizin, Universität Heidelberg, Mannheim
- DKFZ-Hector Krebsinstitut an der Universitätsmedizin Mannheim, Mannheim
- Molecular Medicine Partnership Unit, EMBL, Heidelberg
| | - Wolfgang Fischbach
- Deutsche Gesellschaft zur Bekämpfung der Krankheiten von Magen, Darm und Leber sowie von Störungen des Stoffwechsels und der Ernährung (Gastro-Liga) e. V., Giessen
| | | | - Jens Höppner
- Klinik für Allgemeine Chirurgie, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Lübeck
| | - Dietmar Lorenz
- Chirurgische Klinik I, Allgemein-, Viszeral- und Thoraxchirurgie, Klinikum Darmstadt, Darmstadt
| | - Michael Stahl
- Klinik für Internistische Onkologie und onkologische Palliativmedizin, Evang. Huyssensstiftung, Evang. Kliniken Essen-Mitte, Essen
| | - Martin Stuschke
- Klinik und Poliklinik für Strahlentherapie, Universitätsklinikum Essen, Essen
| | - Oliver Pech
- Klinik für Gastroenterologie und Interventionelle Endoskopie, Krankenhaus Barmherzige Brüder, Regensburg
| | - Udo Vanhoefer
- Klinik für Hämatologie und Onkologie, Katholisches Marienkrankenhaus, Hamburg
| | - Rainer Porschen
- Gastroenterologische Praxis am Kreiskrankenhaus Osterholz, Osterholz-Scharmbeck
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Okamoto K, Yamaguchi T, Asakawa T, Kaida D, Miyata T, Hayashi T, Ojima T, Fujita H, Inaki N, Kinami S, Ninomiya I, Takamura H. Multidisciplinary treatment of advanced cervical esophageal adenocarcinoma derived from a gastric inlet patch: A case report. Oncol Lett 2024; 27:120. [PMID: 38348383 PMCID: PMC10859833 DOI: 10.3892/ol.2024.14253] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2023] [Accepted: 11/21/2023] [Indexed: 02/15/2024] Open
Abstract
A gastric inlet patch (GIP) is an ectopic gastric mucosal lesion usually arising at the cervical esophagus that may rarely cause esophageal adenocarcinoma (EAC). To the best of our knowledge, this is the first case of a GIP-derived EAC that was successfully treated using a multidisciplinary treatment approach. A 64-year-old man was referred to the Department of Gastrointestinal Surgery, Kanazawa University Hospital (Kanazawa, Japan) for surgical treatment of refractory recurrent cervical EAC derived from GIP who had previously been treated with induction chemotherapy, definitive chemoradiotherapy and photodynamic therapy (PDT). Esophagogastroduodenoscopy revealed a stenotic tumor at the GIP site in the cervical esophagus and submucosal tumors with suspected multiple intramural metastases in the anal side of the thoracic esophagus. The patient underwent robot-assisted thoracoscopic esophagectomy with laryngopharyngectomy and cervical lymphadenectomy as radical salvage surgery 4 months after the last PDT procedure. After postoperative adjuvant chemotherapy using oral administration of tegafur/gimeracil/oteracil (oral 5-fluorouracil prodrug) for 1 year; at present, the patient is alive without recurrence 3 years after the operation.
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Affiliation(s)
- Koichi Okamoto
- Department of General and Digestive Surgery, Kanazawa Medical University Hospital, Kahoku, Ishikawa 920-0293, Japan
- Department of Gastrointestinal Surgery, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan
| | - Takahisa Yamaguchi
- Department of Gastroenterological Surgery, Ishikawa Prefectural Central Hospital, Kanazawa, Ishikawa 920-8530, Japan
| | - Tetsuya Asakawa
- Department of Surgery, Houju Memorial Hospital, Nomi, Ishikawa 923-1226, Japan
| | - Daisuke Kaida
- Department of General and Digestive Surgery, Kanazawa Medical University Hospital, Kahoku, Ishikawa 920-0293, Japan
| | - Takashi Miyata
- Department of General and Digestive Surgery, Kanazawa Medical University Hospital, Kahoku, Ishikawa 920-0293, Japan
| | - Tomoyuki Hayashi
- Department of Gastroenterology, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan
| | - Toshihiko Ojima
- Department of Surgery, Toyama Nishi General Hospital, Toyama, Toyama 939-2716, Japan
| | - Hideto Fujita
- Department of General and Digestive Surgery, Kanazawa Medical University Hospital, Kahoku, Ishikawa 920-0293, Japan
| | - Noriyuki Inaki
- Department of Gastrointestinal Surgery, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan
| | - Shinichi Kinami
- Department of General and Digestive Surgery, Kanazawa Medical University Hospital, Kahoku, Ishikawa 920-0293, Japan
| | - Itasu Ninomiya
- Department of Surgery, Fukui Prefectural Hospital, Fukui, Fukui 910-0846, Japan
| | - Hiroyuki Takamura
- Department of General and Digestive Surgery, Kanazawa Medical University Hospital, Kahoku, Ishikawa 920-0293, Japan
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6
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Weusten BLAM, Bisschops R, Dinis-Ribeiro M, di Pietro M, Pech O, Spaander MCW, Baldaque-Silva F, Barret M, Coron E, Fernández-Esparrach G, Fitzgerald RC, Jansen M, Jovani M, Marques-de-Sa I, Rattan A, Tan WK, Verheij EPD, Zellenrath PA, Triantafyllou K, Pouw RE. Diagnosis and management of Barrett esophagus: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy 2023; 55:1124-1146. [PMID: 37813356 DOI: 10.1055/a-2176-2440] [Citation(s) in RCA: 45] [Impact Index Per Article: 22.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/11/2023]
Abstract
MR1 : ESGE recommends the following standards for Barrett esophagus (BE) surveillance:- a minimum of 1-minute inspection time per cm of BE length during a surveillance endoscopy- photodocumentation of landmarks, the BE segment including one picture per cm of BE length, and the esophagogastric junction in retroflexed position, and any visible lesions- use of the Prague and (for visible lesions) Paris classification- collection of biopsies from all visible abnormalities (if present), followed by random four-quadrant biopsies for every 2-cm BE length.Strong recommendation, weak quality of evidence. MR2: ESGE suggests varying surveillance intervals for different BE lengths. For BE with a maximum extent of ≥ 1 cm and < 3 cm, BE surveillance should be repeated every 5 years. For BE with a maximum extent of ≥ 3 cm and < 10 cm, the interval for endoscopic surveillance should be 3 years. Patients with BE with a maximum extent of ≥ 10 cm should be referred to a BE expert center for surveillance endoscopies. For patients with an irregular Z-line/columnar-lined esophagus of < 1 cm, no routine biopsies or endoscopic surveillance are advised.Weak recommendation, low quality of evidence. MR3: ESGE suggests that, if a patient has reached 75 years of age at the time of the last surveillance endoscopy and/or the patient's life expectancy is less than 5 years, the discontinuation of further surveillance endoscopies can be considered. Weak recommendation, very low quality of evidence. MR4: ESGE recommends offering endoscopic eradication therapy using ablation to patients with BE and low grade dysplasia (LGD) on at least two separate endoscopies, both confirmed by a second experienced pathologist.Strong recommendation, high level of evidence. MR5: ESGE recommends endoscopic ablation treatment for BE with confirmed high grade dysplasia (HGD) without visible lesions, to prevent progression to invasive cancer.Strong recommendation, high level of evidence. MR6: ESGE recommends offering complete eradication of all remaining Barrett epithelium by ablation after endoscopic resection of visible abnormalities containing any degree of dysplasia or esophageal adenocarcinoma (EAC).Strong recommendation, moderate quality of evidence. MR7: ESGE recommends endoscopic resection as curative treatment for T1a Barrett's cancer with well/moderate differentiation and no signs of lymphovascular invasion.Strong recommendation, high level of evidence. MR8: ESGE suggests that low risk submucosal (T1b) EAC (i. e. submucosal invasion depth ≤ 500 µm AND no [lympho]vascular invasion AND no poor tumor differentiation) can be treated by endoscopic resection, provided that adequate follow-up with gastroscopy, endoscopic ultrasound (EUS), and computed tomography (CT)/positrion emission tomography-computed tomography (PET-CT) is performed in expert centers.Weak recommendation, low quality of evidence. MR9: ESGE suggests that submucosal (T1b) esophageal adenocarcinoma with deep submucosal invasion (tumor invasion > 500 µm into the submucosa), and/or (lympho)vascular invasion, and/or a poor tumor differentiation should be considered high risk. Complete staging and consideration of additional treatments (chemotherapy and/or radiotherapy and/or surgery) or strict endoscopic follow-up should be undertaken on an individual basis in a multidisciplinary discussion.Strong recommendation, low quality of evidence. MR10 A: ESGE recommends that the first endoscopic follow-up after successful endoscopic eradication therapy (EET) of BE is performed in an expert center.Strong recommendation, very low quality of evidence. B: ESGE recommends careful inspection of the neo-squamocolumnar junction and neo-squamous epithelium with high definition white-light endoscopy and virtual chromoendoscopy during post-EET surveillance, to detect recurrent dysplasia.Strong recommendation, very low level of evidence. C: ESGE recommends against routine four-quadrant biopsies of neo-squamous epithelium after successful EET of BE.Strong recommendation, low level of evidence. D: ESGE suggests, after successful EET, obtaining four-quadrant random biopsies just distal to a normal-appearing neo-squamocolumnar junction to detect dysplasia in the absence of visible lesions.Weak recommendation, low level of evidence. E: ESGE recommends targeted biopsies are obtained where there is a suspicion of recurrent BE in the tubular esophagus, or where there are visible lesions suspicious for dysplasia.Strong recommendation, very low level of evidence. MR11: After successful EET, ESGE recommends the following surveillance intervals:- For patients with a baseline diagnosis of HGD or EAC:at 1, 2, 3, 4, 5, 7, and 10 years after last treatment, after which surveillance may be stopped.- For patients with a baseline diagnosis of LGD:at 1, 3, and 5 years after last treatment, after which surveillance may be stopped.Strong recommendation, low quality of evidence.
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Affiliation(s)
- Bas L A M Weusten
- Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
- Department of Gastroenterology and Hepatology, St. Antonius Hospital Nieuwegein, Nieuwegein, The Netherlands
| | - Raf Bisschops
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, TARGID, Leuven, Belgium
| | - Mario Dinis-Ribeiro
- Department of Gastroenterology, Porto Comprehensive Cancer Center, and RISE@CI-IPOP (Health Research Network), Porto Portugal
| | - Massimiliano di Pietro
- Early Cancer Institute, University of Cambridge and Department of Gastroenterology, Cambridge University Hospitals NHS Trust, Cambridge, UK
| | - Oliver Pech
- Department of Gastroenterology and Interventional Endoscopy, St. John of God Hospital, Regensburg, Germany
| | - Manon C W Spaander
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Francisco Baldaque-Silva
- Advanced Endoscopy Center Carlos Moreira da Silva, Department of Gastroenterology, Pedro Hispano Hospital, Matosinhos, Portugal
- Division of Medicine, Department of Upper Gastrointestinal Diseases, Karolinska University Hospital and Karolinska Institute, Stockholm, Sweden
| | - Maximilien Barret
- Department of Gastroenterology and Digestive Oncology, Cochin Hospital and University of Paris, Paris, France
| | - Emmanuel Coron
- Institut des Maladies de l'Appareil Digestif, IMAD, Centre hospitalier universitaire Hôtel-Dieu, Nantes, Nantes, France
- Department of Gastroenterology and Hepatology, University Hospital of Geneva (HUG), Geneva, Switzerland
| | - Glòria Fernández-Esparrach
- Endoscopy Unit, Department of Gastroenterology, Hospital Clínic of Barcelona, University of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Biomedical Research Network on Hepatic and Digestive Diseases (CIBEREHD), Barcelona, Spain
| | - Rebecca C Fitzgerald
- Early Cancer Institute, University of Cambridge and Department of Gastroenterology, Cambridge University Hospitals NHS Trust, Cambridge, UK
| | - Marnix Jansen
- Department of Histopathology, University College London Hospital NHS Trust, London, UK
| | - Manol Jovani
- Division of Gastroenterology, Maimonides Medical Center, New York, New York, USA
| | - Ines Marques-de-Sa
- Department of Gastroenterology, Porto Comprehensive Cancer Center, and RISE@CI-IPOP (Health Research Network), Porto Portugal
| | - Arti Rattan
- Department of Gastroenterology, Wollongong Hospital, Wollongong, New South Wales, Australia
| | - W Keith Tan
- Early Cancer Institute, University of Cambridge and Department of Gastroenterology, Cambridge University Hospitals NHS Trust, Cambridge, UK
| | - Eva P D Verheij
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers location University of Amsterdam, Amsterdam Gastroenterology, Endocrinology and Metabolism, Cancer Center Amsterdam, Amsterdam, The Netherlands
| | - Pauline A Zellenrath
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Konstantinos Triantafyllou
- Hepatogastroenterology Unit, Second Department of Propaedeutic Internal Medicine, Medical School, National and Kapodistrian University of Athens, Attikon University General Hospital, Athens, Greece
| | - Roos E Pouw
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers location University of Amsterdam, Amsterdam Gastroenterology, Endocrinology and Metabolism, Cancer Center Amsterdam, Amsterdam, The Netherlands
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Lin YT, Zhou CC, Xu K, Zhang MD, Li X. Cost-effectiveness analysis of serplulimab in combination with cisplatin plus 5-fluorouracil chemotherapy compared to cisplatin plus 5-fluorouracil chemotherapy as first-line treatment for advanced or metastatic esophageal squamous cell carcinoma in China. Ther Adv Med Oncol 2023; 15:17588359231213621. [PMID: 38028139 PMCID: PMC10666699 DOI: 10.1177/17588359231213621] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2023] [Accepted: 10/24/2023] [Indexed: 12/01/2023] Open
Abstract
Background This study evaluated the cost-effectiveness of serplulimab plus chemotherapy versus chemotherapy alone in treating advanced/metastatic esophageal squamous cell carcinoma (ESCC) within the Chinese health care system. Methods A partitioned survival model based on ASTRUM-007 trial patient characteristics was developed. Efficacy, safety, and medical/economic data were obtained from the trial and real-world clinical practice. Costs, quality-adjusted life years (QALY), and incremental cost-effectiveness ratios (ICERs) were calculated for both treatment strategies. Sensitivity, subgroup, and scenario analyses were performed to assess the uncertainty impact. Results Serplulimab combined with chemotherapy yielded an ICER of US$ 53,538.27/QALY. Deterministic sensitivity analysis identified patient survival and serplulimab price as influential parameters. Probabilistic sensitivity analysis showed a 47.33% probability of cost-effectiveness at a willingness-to-pay (WTP) threshold of US$ 53,541/QALY and 0.05% at three times China's GDP per capita. Subgroup analysis revealed that patients with a programmed death-ligand 1 (PD-L1) expression combined positive score (CPS) ⩾10 had a lower hazard ratio (0.59) and ICER (US$ 29,935.23/QALY), with a 95.36% probability of cost-effectiveness. Scenario analysis demonstrated that the drug donation discount policy significantly increased the likelihood of cost-effective serplulimab-chemotherapy combinations in Jiangsu, Fujian, and Guangdong at 99.99%, 99.90%, and 94.16%, respectively. Conclusion Compared to chemotherapy alone, serplulimab combined with chemotherapy is currently not a cost-effective first-line treatment for advanced/metastatic ESCC in China. However, as serplulimab plus chemotherapy regimens evolve and price competition among programmed death 1 (PD-1) inhibitors intensifies, this combination may become a cost-effective treatment option.
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Affiliation(s)
- Ying-Tao Lin
- Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China
- Department of Drug Clinical Trial Institution, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian, China
- Department of Pharmaceutical Regulatory Science and Pharmacoeconomics, School of Pharmacy, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Chong-Chong Zhou
- Department of Pharmaceutical Regulatory Science and Pharmacoeconomics, School of Pharmacy, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Kai Xu
- Department of Pharmaceutical Regulatory Science and Pharmacoeconomics, School of Pharmacy, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Meng-Die Zhang
- Department of Pharmaceutical Regulatory Science and Pharmacoeconomics, School of Pharmacy, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Xin Li
- Center for Global Health, School of Public Health, Nanjing Medical University, No.101 Longmian Avenue, Nanjing, Jiangsu 210029, China
- Department of Pharmaceutical Regulatory Science and Pharmacoeconomics, School of Pharmacy, Nanjing Medical University, No.101 Longmian Avenue, Nanjing, Jiangsu, China
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8
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Li S, Hoefnagel SJM, Krishnadath KK. Molecular Biology and Clinical Management of Esophageal Adenocarcinoma. Cancers (Basel) 2023; 15:5410. [PMID: 38001670 PMCID: PMC10670638 DOI: 10.3390/cancers15225410] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2023] [Revised: 11/10/2023] [Accepted: 11/12/2023] [Indexed: 11/26/2023] Open
Abstract
Esophageal adenocarcinoma (EAC) is a highly lethal malignancy. Due to its rising incidence, EAC has become a severe health challenge in Western countries. Current treatment strategies are mainly chosen based on disease stage and clinical features, whereas the biological background is hardly considered. In this study, we performed a comprehensive review of existing studies and discussed how etiology, genetics and epigenetic characteristics, together with the tumor microenvironment, contribute to the malignant behavior and dismal prognosis of EAC. During the development of EAC, several intestinal-type proteins and signaling cascades are induced. The anti-inflammatory and immunosuppressive microenvironment is associated with poor survival. The accumulation of somatic mutations at the early phase and chromosomal structural rearrangements at relatively later time points contribute to the dynamic and heterogeneous genetic landscape of EAC. EAC is also characterized by frequent DNA methylation and dysregulation of microRNAs. We summarize the findings of dysregulations of specific cytokines, chemokines and immune cells in the tumor microenvironment and conclude that DNA methylation and microRNAs vary with each different phase of BE, LGD, HGD, early EAC and invasive EAC. Furthermore, we discuss the suitability of the currently employed therapies in the clinic and possible new therapies in the future. The development of targeted and immune therapies has been hampered by the heterogeneous genetic characteristics of EAC. In view of this, the up-to-date knowledge revealed by this work is absolutely important for future EAC studies and the discovery of new therapeutics.
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Affiliation(s)
- Shulin Li
- Center for Experimental and Molecular Medicine, Amsterdam University Medical Centers, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands;
- Cancer Center Amsterdam, 1081 HV Amsterdam, The Netherlands
| | | | - Kausilia Krishnawatie Krishnadath
- Department of Gastroenterology and Hepatology, Antwerp University Hospital, 2650 Edegem, Belgium
- Laboratory of Experimental Medicine and Pediatrics, University of Antwerp, 2000 Antwerpen, Belgium
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9
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Authors, und die Mitarbeiter der Leitlinienkommission, Collaborators:. S3-Leitlinie Diagnostik und Therapie der Plattenepithelkarzinome und Adenokarzinome des Ösophagus. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2023; 61:e209-e307. [PMID: 37285869 DOI: 10.1055/a-1771-6953] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/09/2023]
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10
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Overchuk M, Weersink RA, Wilson BC, Zheng G. Photodynamic and Photothermal Therapies: Synergy Opportunities for Nanomedicine. ACS NANO 2023; 17:7979-8003. [PMID: 37129253 PMCID: PMC10173698 DOI: 10.1021/acsnano.3c00891] [Citation(s) in RCA: 393] [Impact Index Per Article: 196.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 05/03/2023]
Abstract
Tumoricidal photodynamic (PDT) and photothermal (PTT) therapies harness light to eliminate cancer cells with spatiotemporal precision by either generating reactive oxygen species or increasing temperature. Great strides have been made in understanding biological effects of PDT and PTT at the cellular, vascular and tumor microenvironmental levels, as well as translating both modalities in the clinic. Emerging evidence suggests that PDT and PTT may synergize due to their different mechanisms of action, and their nonoverlapping toxicity profiles make such combination potentially efficacious. Moreover, PDT/PTT combinations have gained momentum in recent years due to the development of multimodal nanoplatforms that simultaneously incorporate photodynamically- and photothermally active agents. In this review, we discuss how combining PDT and PTT can address the limitations of each modality alone and enhance treatment safety and efficacy. We provide an overview of recent literature featuring dual PDT/PTT nanoparticles and analyze the strengths and limitations of various nanoparticle design strategies. We also detail how treatment sequence and dose may affect cellular states, tumor pathophysiology and drug delivery, ultimately shaping the treatment response. Lastly, we analyze common experimental design pitfalls that complicate preclinical assessment of PDT/PTT combinations and propose rational guidelines to elucidate the mechanisms underlying PDT/PTT interactions.
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Affiliation(s)
- Marta Overchuk
- Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario M5G 1L7, Canada
- Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Chapel Hill, North Carolina 27599, United States
| | - Robert A Weersink
- Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario M5G 1L7, Canada
- Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5G 1L7, Canada
- Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario M5G 1L7, Canada
- Department of Radiation Oncology, University of Toronto, Toronto, Ontario M5G 1L7, Canada
| | - Brian C Wilson
- Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario M5G 1L7, Canada
- Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5G 1L7, Canada
| | - Gang Zheng
- Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario M5G 1L7, Canada
- Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5G 1L7, Canada
- Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario M5G 1L7, Canada
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11
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Bartusik-Aebisher D, Osuchowski M, Adamczyk M, Stopa J, Cieślar G, Kawczyk-Krupka A, Aebisher D. Advancements in photodynamic therapy of esophageal cancer. Front Oncol 2022; 12:1024576. [PMID: 36465381 PMCID: PMC9713848 DOI: 10.3389/fonc.2022.1024576] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2022] [Accepted: 10/24/2022] [Indexed: 12/02/2023] Open
Abstract
The poor prognosis of patients with esophageal cancer leads to the constant search for new ways of treatment of this disease. One of the methods used in high-grade dysplasia, superficial invasive carcinoma, and sometimes palliative care is photodynamic therapy (PDT). This method has come a long way from the first experimental studies to registration in the treatment of esophageal cancer and is constantly being improved and refined. This review describes esophageal cancer, current treatment methods, the introduction to PDT, the photosensitizers (PSs) used in esophageal carcinoma PDT, PDT in squamous cell carcinoma (SCC) of the esophagus, and PDT in invasive adenocarcinoma of the esophagus. For this review, research and review articles from PubMed and Web of Science databases were used. The keywords used were "photodynamic therapy in esophageal cancer" in the years 2000-2020. The total number of papers returned was 1,000. After the review was divided into topic blocks and the searched publications were analyzed, 117 articles were selected.
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Affiliation(s)
- Dorota Bartusik-Aebisher
- Department of Biochemistry and General Chemistry, Medical College of The University of Rzeszów, Rzeszów, Poland
| | | | - Marta Adamczyk
- Medical Faculty, Medical University of Warsaw, Warsaw, Poland
| | - Joanna Stopa
- Medical College of The University of Rzeszów, Rzeszów, Poland
| | - Grzegorz Cieślar
- Department of Internal Medicine, Angiology, and Physical Medicine, Center for Laser Diagnostics and Therapy, Medical University of Silesia in Katowice, Bytom, Poland
| | - Aleksandra Kawczyk-Krupka
- Department of Internal Medicine, Angiology, and Physical Medicine, Center for Laser Diagnostics and Therapy, Medical University of Silesia in Katowice, Bytom, Poland
| | - David Aebisher
- Department of Photomedicine and Physical Chemistry, Medical College of The University of Rzeszów, Rzeszów, Poland
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12
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Lv G, Dong Z, Zhao Y, Ma N, Jiang X, Li J, Wang J, Wang J, Zhang W, Lin X, Hu Z. Precision Killing of Sinoporphyrin Sodium-Mediated Photodynamic Therapy against Malignant Tumor Cells. Int J Mol Sci 2022; 23:10561. [PMID: 36142474 PMCID: PMC9503352 DOI: 10.3390/ijms231810561] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2022] [Revised: 08/29/2022] [Accepted: 09/09/2022] [Indexed: 11/26/2022] Open
Abstract
Photodynamic therapy (PDT) has significant advantages in the treatment of malignant tumors, such as high efficiency, minimal invasion and less side effects, and it can preserve the integrity and quality of the organs. The power density, irradiation time and photosensitizer (PS) concentration are three main parameters that play important roles in killing tumor cells. However, until now, the underlying relationships among them for PDT outcomes have been unclear. In this study, human malignant glioblastoma U-118MG and melanoma A375 cells were selected, and the product of the power density, irradiation time and PS concentration was defined as the total photodynamic parameter (TPP), in order to investigate the mechanisms of PS sinoporphyrin sodium (DVDMS)-mediated PDT (DVDMS-PDT). The results showed that the survival rates of the U-118MG and A375 cells were negatively correlated with the TPP value in the curve, and the correlation exactly filed an e-exponential function. Moreover, according to the formula, we realized controllable killing effects of the tumor cells by randomly adjusting the three parameters, and we finally verified the accuracy and repeatability of the formula. In conclusion, the establishment and implementation of a newly functional relationship among the PDT parameters are essential for predicting PDT outcomes and providing personalized precise treatment, and they are contributive to the development of PDT dosimetry.
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Affiliation(s)
- Guixiang Lv
- Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin 150086, China
| | - Zhihui Dong
- Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin 150086, China
| | - Yunhan Zhao
- Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin 150086, China
| | - Ning Ma
- Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin 150086, China
| | - Xiaochen Jiang
- Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin 150086, China
| | - Jia Li
- Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin 150086, China
| | - Jinyue Wang
- Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin 150086, China
| | - Jiaxin Wang
- Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin 150086, China
| | - Wenxiu Zhang
- Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin 150086, China
| | - Xin Lin
- Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin 150086, China
| | - Zheng Hu
- Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin 150086, China
- Laboratory of Sono- and Photo-Theranostic Technologies, Harbin Institute of Technology, Harbin 150080, China
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13
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Wolfson P, Ho KMA, Wilson A, McBain H, Hogan A, Lipman G, Dunn J, Haidry R, Novelli M, Olivo A, Lovat LB. Endoscopic eradication therapy for Barrett's esophagus-related neoplasia: a final 10-year report from the UK National HALO Radiofrequency Ablation Registry. Gastrointest Endosc 2022; 96:223-233. [PMID: 35189088 DOI: 10.1016/j.gie.2022.02.016] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Accepted: 02/09/2022] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS Long-term durability data for effectiveness of radiofrequency ablation (RFA) to prevent esophageal adenocarcinoma in patients with dysplastic Barrett's esophagus (BE) are lacking. METHODS We prospectively collected data from 2535 patients with BE (mean length, 5.2 cm; range, 1-20) and neoplasia (20% low-grade dysplasia, 54% high-grade dysplasia, 26% intramucosal carcinoma) who underwent RFA therapy across 28 UK hospitals. We assessed rates of invasive cancer and performed detailed analyses of 1175 patients to assess clearance rates of dysplasia (CR-D) and intestinal metaplasia (CR-IM) within 2 years of starting RFA therapy. We assessed relapses and rates of return to CR-D (CR-D2) and CR-IM (CR-IM2) after further therapy. CR-D and CR-IM were confirmed by an absence of dysplasia and intestinal metaplasia on biopsy samples taken at 2 consecutive endoscopies. RESULTS Ten years after starting treatment, the Kaplan-Meier (KM) cancer rate was 4.1% with a crude incidence rate of .52 per 100 patient-years. CR-D and CR-IM after 2 years of therapy were 88% and 62.6%, respectively. KM relapse rates were 5.9% from CR-D and 18.7% from CR-IM at 8 years, with most occurring in the first 2 years. Both were successfully retreated with rates of CR-D2 of 63.4% and CR-IM2 of 70.0% 2 years after retreatment. EMR before RFA increased the likelihood of rescue EMR from 17.2% to 41.7% but did not affect the rate of CR-D, whereas rescue EMR after RFA commenced reduced CR-D from 91.4% to 79.7% (χ2P < .001). CONCLUSIONS RFA treatment is effective and durable to prevent esophageal adenocarcinoma. Most treatment relapses occur early and can be successfully retreated.
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Affiliation(s)
- Paul Wolfson
- Wellcome/EPSRC Centre for Interventional & Surgical Sciences, University College London, London, UK; Division of Surgery and Interventional Sciences, University College London, London, UK
| | - Kai Man Alexander Ho
- Wellcome/EPSRC Centre for Interventional & Surgical Sciences, University College London, London, UK; Division of Surgery and Interventional Sciences, University College London, London, UK; Gastrointestinal Services, University College London Hospital, London, UK
| | - Ash Wilson
- Division of Surgery and Interventional Sciences, University College London, London, UK
| | - Hazel McBain
- Gastrointestinal Services, University College London Hospital, London, UK
| | - Aine Hogan
- Division of Surgery and Interventional Sciences, University College London, London, UK
| | - Gideon Lipman
- Division of Surgery and Interventional Sciences, University College London, London, UK
| | - Jason Dunn
- Division of Surgery and Interventional Sciences, University College London, London, UK
| | - Rehan Haidry
- Division of Surgery and Interventional Sciences, University College London, London, UK; Gastrointestinal Services, University College London Hospital, London, UK
| | - Marco Novelli
- Research Department of Pathology, Cancer Institute, University College London Hospital, London, UK
| | - Alessandro Olivo
- Wellcome/EPSRC Centre for Interventional & Surgical Sciences, University College London, London, UK
| | - Laurence B Lovat
- Wellcome/EPSRC Centre for Interventional & Surgical Sciences, University College London, London, UK; Division of Surgery and Interventional Sciences, University College London, London, UK; Gastrointestinal Services, University College London Hospital, London, UK
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14
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Paiji C, Sedarat A. Endoscopic Management of Esophageal Cancer. Cancers (Basel) 2022; 14:cancers14153583. [PMID: 35892840 PMCID: PMC9329770 DOI: 10.3390/cancers14153583] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2022] [Revised: 07/18/2022] [Accepted: 07/20/2022] [Indexed: 02/04/2023] Open
Abstract
Advances in technology and improved understanding of the pathobiology of esophageal cancer have allowed endoscopy to serve a growing role in the management of this disease. Precursor lesions can be detected using enhanced diagnostic modalities and eradicated with ablation therapy. Furthermore, evolution in endoscopic resection has provided larger specimens for improved diagnostic accuracy and offer potential for cure of early esophageal cancer. In patients with advanced esophageal cancer, endoluminal therapy can improve symptom burden and provide therapeutic options for complications such as leaks, perforations, and fistulas. The purpose of this review article is to highlight the role of endoscopy in the diagnosis, treatment, and palliation of esophageal cancer.
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15
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Lin YT, Liu TX, Chen J, Wang C, Chen Y. Cost-Effectiveness of Nivolumab Immunotherapy vs. Paclitaxel or Docetaxel Chemotherapy as Second-Line Therapy in Advanced Esophageal Squamous Cell Carcinoma in China. Front Public Health 2022; 10:923619. [PMID: 35844891 PMCID: PMC9277084 DOI: 10.3389/fpubh.2022.923619] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2022] [Accepted: 06/09/2022] [Indexed: 12/24/2022] Open
Abstract
This study aimed to evaluate and compare nivolumab's cost-effectiveness with chemotherapy in patients with advanced esophageal squamous cell carcinoma from the Chinese healthcare system perspective. To this end, the researchers utilized a partitioned survival model with three mutually exclusive health stages. The characteristics of the patients used as inclusion and exclusion criteria in this model were the same as those used for patients with advanced esophageal squamous cell carcinoma in the ATTRACTION-3 study. The ATTRACTION-3 trial, which took place between January 7, 2016 and November 12, 2018, also yielded important clinical data. Data on medical and economic preferences were collected from real-world clinical practices. Costs, quality-adjusted life years, and incremental cost-effectiveness ratio were calculated for the two therapy options. The model uncertainty was investigated using a deterministic and probabilistic sensitivity analysis. When compared to chemotherapy, nivolumab was linked with an increase of 0.28 quality-adjusted life years with an increased cost of US$ 36,956.81 per patient in the base case analysis of a hypothetical sample of 419 patients. The incremental cost-effectiveness ratio in the deterministic sensitivity analysis was US$ 132,029.46/quality-adjusted life year, with a 48.02% probability of being cost-effective at willingness-to-pay thresholds of US$ 132,029.22/quality-adjusted life year. The incremental cost-effectiveness ratio remained greater than US$ 80,000/quality-adjusted life year in the deterministic sensitivity analyses. To be more cost-effective and remain below the threshold of 37,653 US$/quality-adjusted life year, which the Chinese population can afford, nivolumab's price would have to be lowered sharply by 53.50%. Nivolumab is clinically beneficial but not cost-effective when compared to chemotherapy. A substantial reduction in nivolumab's drug acquisition cost would be necessary to make it cost-effective for immunotherapy.
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Affiliation(s)
- Ying-tao Lin
- Department of Drug Clinical Trial Administration Office, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, China
| | - Tian-xiu Liu
- Department of Thoracic Radiotherapy, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, China
| | - Jian Chen
- Department of Surgical Oncology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, China
| | - Chang Wang
- Department of Medical Oncology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, China
| | - Ying Chen
- Department of Drug Clinical Trial Administration Office, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, China
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16
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Cheruku RR, Turowski SG, Durrani FA, Tabaczynski WA, Cacaccio J, Missert JR, Curtin L, Sexton S, Alberico R, Hendler CM, Spernyak JA, Grossman Z, Pandey RK. Tumor-Avid 3-(1'-Hexyloxy)ethyl-3-devinylpyrpyropheophorbide-a (HPPH)-3Gd(III)tetraxetan (DOTA) Conjugate Defines Primary Tumors and Metastases. J Med Chem 2022; 65:9267-9280. [PMID: 35763292 DOI: 10.1021/acs.jmedchem.2c00547] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
3-(1'-Hexyloxyethyl)-3-devinylpyropheophorbide-a (HPPH or Photochlor), a tumor-avid chlorophyll a derivative currently undergoing human clinical trials, was conjugated with mono-, di-, and tri-Gd(III)tetraxetan (DOTA) moieties. The T1/T2 relaxivity and in vitro PDT efficacy of these conjugates were determined. The tumor specificity of the most promising conjugate was also investigated at various time points in mice and rats bearing colon tumors, as well as rabbits bearing widespread metastases from VX2 systemic arterial disseminated metastases. All the conjugates showed significant T1 and T2 relaxivities. However, the conjugate containing 3-Gd(III)-aminoethylamido-DOTA at position 17 of HPPH demonstrated great potential for tumor imaging by both MR and fluorescence while maintaining its PDT efficacy. At an MR imaging dose (10 μmol/kg), HPPH-3Gd(III)DOTA did not cause any significant organ toxicity in mice, indicating its potential as a cancer imaging (MR and fluorescence) agent with an option to treat cancer by photodynamic therapy (PDT).
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Affiliation(s)
- Ravindra R Cheruku
- Photodynamic Therapy Center, Cell Stress Biology, Roswell Park Comprehensive Cancer Center, Buffalo, New York 14263, United States
| | - Steven G Turowski
- Translational Imaging Shared Resource, Cell Stress Biology, Roswell Park Comprehensive Cancer Center, Buffalo, New York 14263, United States
| | - Farukh A Durrani
- Photodynamic Therapy Center, Cell Stress Biology, Roswell Park Comprehensive Cancer Center, Buffalo, New York 14263, United States
| | - Walter A Tabaczynski
- Photodynamic Therapy Center, Cell Stress Biology, Roswell Park Comprehensive Cancer Center, Buffalo, New York 14263, United States
| | - Joseph Cacaccio
- Photodynamic Therapy Center, Cell Stress Biology, Roswell Park Comprehensive Cancer Center, Buffalo, New York 14263, United States
| | - Joseph R Missert
- Photodynamic Therapy Center, Cell Stress Biology, Roswell Park Comprehensive Cancer Center, Buffalo, New York 14263, United States
| | - Leslie Curtin
- Department of Laboratory Animal Resources (DLAR), Roswell Park Comprehensive Cancer Center, Buffalo, New York 14263, United States
| | - Sandra Sexton
- Department of Laboratory Animal Resources (DLAR), Roswell Park Comprehensive Cancer Center, Buffalo, New York 14263, United States
| | - Ronald Alberico
- Department of Radiology, Roswell Park Comprehensive Cancer Center, Buffalo, New York 14263, United States
| | - Craig M Hendler
- Department of Radiology, Roswell Park Comprehensive Cancer Center, Buffalo, New York 14263, United States
| | - Joseph A Spernyak
- Translational Imaging Shared Resource, Cell Stress Biology, Roswell Park Comprehensive Cancer Center, Buffalo, New York 14263, United States
| | - Zachary Grossman
- Department of Radiology, Roswell Park Comprehensive Cancer Center, Buffalo, New York 14263, United States
| | - Ravindra K Pandey
- Photodynamic Therapy Center, Cell Stress Biology, Roswell Park Comprehensive Cancer Center, Buffalo, New York 14263, United States
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17
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Ventre S, Shahid H. Endoscopic therapies for Barrett's esophagus. Transl Gastroenterol Hepatol 2021; 6:62. [PMID: 34805584 DOI: 10.21037/tgh.2020.02.04] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2019] [Accepted: 01/23/2020] [Indexed: 11/06/2022] Open
Abstract
The management of Barrett's esophagus (BE) has evolved as newer technologies and novel methods are developed. Endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) are the initial interventions of choice for nodular BE, with ESD reserved for endoscopists highly trained in the technique and for larger lesions that would warrant en bloc resection. Resection should then be followed by ablative therapy, which remains first line in the treatment of BE with dysplasia. Although there is a myriad of ablation techniques available to the endoscopist, this review has found that radiofrequency ablation (RFA) continues to have the most robust safety and efficacy data to support its use despite a relatively high rate of recurrence. Cryotherapy and Hybrid-APC appear to be safe and effective as RFA alternatives, but further trials are still needed to directly compare their outcomes to RFA and ultimately guide changes in treatment decisions.
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Affiliation(s)
- Scott Ventre
- Department of Medicine, Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ, USA
| | - Haroon Shahid
- Division of Gastroenterology & Hepatology, Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ, USA
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18
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Almeida J, Zhang G, Wang M, Queirós C, Cerqueira AFR, Tomé AC, Barone G, Vicente MGH, Hey-Hawkins E, Silva AMG, Rangel M. Synthesis, characterization, and cellular investigations of porphyrin- and chlorin-indomethacin conjugates for photodynamic therapy of cancer. Org Biomol Chem 2021; 19:6501-6512. [PMID: 34254099 DOI: 10.1039/d1ob01015h] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Indomethacin is a potent non-steroidal anti-inflammatory drug (NSAID) with a strong selective inhibitor activity towards cyclooxygenase-2 (COX-2), an enzyme that is highly overexpressed in various tumour cells, being involved in tumourigenesis. Concomitantly, porphyrins have gained much attention as promising photosensitizers (PSs) for the non-invasive photodynamic therapy (PDT) of cancer. Herein, we report the design, and determine the singlet oxygen generation capacity and in vitro cellular toxicity of porphyrin- and chlorin-indomethacin conjugates (P2-Ind and C2-Ind). Both the conjugates were obtained in high yields and were characterized by 1H, 19F and 13C NMR as well as by high resolution mass spectrometry. The singlet oxygen generation properties were assessed by the 1,3-diphenylisobenzofuran singlet oxygen trap method, which showed that C2 and C2-Ind are the best singlet oxygen photosensitizers. In addition, it was found that the presence of indomethacin did not influence the singlet oxygen generation of porphyrin or chlorin. Cytotoxicity studies of the conjugate in human HEp2 cells revealed that the porphyrin- and chlorin-indomethacin conjugates have similar dark cytotoxicities, while chlorin C2 was shown to be the most phototoxic. Despite having lower cellular uptake than C2-Ind after 24 hours, chlorin C2 had a broad localization in HEp2 cells while the chlorin-indomethacin conjugate C2-Ind could be detected in the form of small aggregates. DFT calculations were performed to shed light on the reaction energy involved in the formation of the indomethacin conjugates and to compare the relative stability of selected isomers in solution. Moreover, the calculated energy of their first excited triplet state structures confirmed their use as suitable photosensitizers to generate singlet oxygen for PDT.
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Affiliation(s)
- José Almeida
- LAQV-REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências da Universidade do Porto, 4169-007 Porto, Portugal.
| | - Guanyu Zhang
- Department of Chemistry, Louisiana State University, Baton Rouge, LA 70803, USA
| | - Maodie Wang
- Department of Chemistry, Louisiana State University, Baton Rouge, LA 70803, USA
| | - Carla Queirós
- LAQV-REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências da Universidade do Porto, 4169-007 Porto, Portugal.
| | - Ana F R Cerqueira
- LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal
| | - Augusto C Tomé
- LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal
| | - Giampaolo Barone
- Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche, Università di Palermo, Viale delle Scienze, Edificio 17, 90128 Palermo, Italy
| | - M Graça H Vicente
- Department of Chemistry, Louisiana State University, Baton Rouge, LA 70803, USA
| | - Evamarie Hey-Hawkins
- Institute of Inorganic Chemistry, Faculty of Chemistry and Mineralogy, Leipzig University, Johannisallee 29, 04103 Leipzig, Germany
| | - Ana M G Silva
- LAQV-REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências da Universidade do Porto, 4169-007 Porto, Portugal.
| | - Maria Rangel
- LAQV-REQUIMTE, Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, 4099-003 Porto, Portugal
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19
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Yassine AA, Lilge L, Betz V. Optimizing Interstitial Photodynamic Therapy Planning With Reinforcement Learning-Based Diffuser Placement. IEEE Trans Biomed Eng 2021; 68:1668-1679. [PMID: 33471748 DOI: 10.1109/tbme.2021.3053197] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Abstract
Interstitial photodynamic therapy (iPDT) has shown promising results recently as a minimally invasive stand-alone or intra-operative cancer treatment. The development of non-toxic photosensitizing drugs with improved target selectivity has increased its efficacy. However, personalized treatment planning that determines the number of photon emitters, their positions and their input powers while taking into account tissue anatomy and treatment response is still lacking to further improve outcomes. OBJECTIVE To develop new algorithms that generate high-quality plans by optimizing over the light source positions, along with their powers, to minimize the damage to organs-at-risk while eradicating the tumor. The optimization algorithms should also accurately model the physics of light propagation through the use of Monte-Carlo simulators. METHODS We use simulated-annealing as a baseline algorithm to place the sources. We propose different source perturbations that are likely to provide better outcomes and study their impact. To minimize the number of moves attempted (and effectively runtime) without degrading result quality, we use a reinforcement learning-based method to decide which perturbation strategy to perform in each iteration. We simulate our algorithm on virtual brain tumors modeling real glioblastoma multiforme cases, assuming a 5-ALA PpIX induced photosensitizer that is activated at [Formula: see text] wavelength. RESULTS The algorithm generates plans that achieve an average of 46% less damage to organs-as-risk compared to the manual placement used in current clinical studies. SIGNIFICANCE Having a general and high-quality planning system makes iPDT more effective and applicable to a wider variety of oncological indications. This paves the way for more clinical trials.
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20
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Abstract
The incidence of esophageal cancer (EC) is on the rise. With the distinct subtypes of adenocarcinoma and squamous cell carcinoma comes specific risk factors, and as a result, people of certain regions of the world can be more prone to a subtype. For example, squamous cell carcinoma of the esophagus has the highest incidence in eastern Africa and eastern Asia, with smoking being a major risk factor, whereas adenocarcinoma is more prevalent in North America and western Europe, with gastroesophageal reflux disease being a leading risk factor. With that being said, adenocarcinoma and squamous cell carcinoma have similar and unfortunately poor survival rates, partly because EC is prone to early metastasis given that the esophagus does not have a serosa, as well as the superficial nature of its lymphatics compared with the rest of the gastrointestinal tract. This makes early detection of the utmost importance, and certain patients have been shown to have the benefit of screening/surveillance endoscopies, including those with Barrett's esophagus, lye-induced/caustic strictures, tylosis, and Peutz-Jeghers syndrome. Until treatments significantly improve, identifying EC at the earliest stage will have the best success for patient outcomes, and further elucidation of its pathogenesis and risk factors may lead to identifying other high-risk groups that should be screened.
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Affiliation(s)
- Michael DiSiena
- From the Division of Gastroenterology and Hepatology, University of Connecticut Health Center, Farmington
| | - Alexander Perelman
- From the Division of Gastroenterology and Hepatology, University of Connecticut Health Center, Farmington
| | - John Birk
- From the Division of Gastroenterology and Hepatology, University of Connecticut Health Center, Farmington
| | - Houman Rezaizadeh
- From the Division of Gastroenterology and Hepatology, University of Connecticut Health Center, Farmington
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21
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Mochizuki C, Nakamura J, Nakamura M. Development of Non-Porous Silica Nanoparticles towards Cancer Photo-Theranostics. Biomedicines 2021; 9:73. [PMID: 33451074 PMCID: PMC7828543 DOI: 10.3390/biomedicines9010073] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2021] [Accepted: 01/09/2021] [Indexed: 02/07/2023] Open
Abstract
Nanoparticles have demonstrated several advantages for biomedical applications, including for the development of multifunctional agents as innovative medicine. Silica nanoparticles hold a special position among the various types of functional nanoparticles, due to their unique structural and functional properties. The recent development of silica nanoparticles has led to a new trend in light-based nanomedicines. The application of light provides many advantages for in vivo imaging and therapy of certain diseases, including cancer. Mesoporous and non-porous silica nanoparticles have high potential for light-based nanomedicine. Each silica nanoparticle has a unique structure, which incorporates various functions to utilize optical properties. Such advantages enable silica nanoparticles to perform powerful and advanced optical imaging, from the in vivo level to the nano and micro levels, using not only visible light but also near-infrared light. Furthermore, applications such as photodynamic therapy, in which a lesion site is specifically irradiated with light to treat it, have also been advancing. Silica nanoparticles have shown the potential to play important roles in the integration of light-based diagnostics and therapeutics, termed "photo-theranostics". Here, we review the recent development and progress of non-porous silica nanoparticles toward cancer "photo-theranostics".
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Affiliation(s)
- Chihiro Mochizuki
- Department of Organ Anatomy & Nanomedicine, Graduate School of Medicine, Yamaguchi University, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan; (C.M.); (J.N.)
- Core Clusters for Research Initiatives of Yamaguchi University, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan
| | - Junna Nakamura
- Department of Organ Anatomy & Nanomedicine, Graduate School of Medicine, Yamaguchi University, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan; (C.M.); (J.N.)
- Core Clusters for Research Initiatives of Yamaguchi University, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan
| | - Michihiro Nakamura
- Department of Organ Anatomy & Nanomedicine, Graduate School of Medicine, Yamaguchi University, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan; (C.M.); (J.N.)
- Core Clusters for Research Initiatives of Yamaguchi University, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan
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22
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Sullivan R, Mulki R, Peter S. The role of ablation in the treatment of dysplastic Barrett's esophagus. Ther Adv Gastrointest Endosc 2021; 14:26317745211049967. [PMID: 34708203 PMCID: PMC8544766 DOI: 10.1177/26317745211049967] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Accepted: 09/07/2021] [Indexed: 12/15/2022] Open
Abstract
Endoscopic eradication therapy for Barrett's esophagus has been established as an effective management strategy for patients with Barrett's esophagus with dysplasia and early esophageal cancer. Among the endoscopic therapies, ablation techniques such as radiofrequency ablation and cryoablation are effective primary treatment interventions with acceptable low complication rates forming the spectrum of a multimodal approach. Appropriate selection of patients, high-definition endoscopic evaluation, and dedicated histological assessment are important cornerstones to help navigate to the best effective treatment method. Carefully structured surveillance programs and preventive measures will be needed to provide long-term durability for maintaining complete remission.
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Affiliation(s)
- Rebecca Sullivan
- Division of Gastroenterology and Hepatology, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Ramzi Mulki
- Division of Gastroenterology and Hepatology, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Shajan Peter
- Associate Professor, Basil Hirschowitz Endoscopic Centre of Endoscopic Excellence, Division of Gastroenterology and Hepatology, University of Alabama at Birmingham, 6th Floor Jefferson Tower, 625 19th Street South, Birmingham, AL 35249, USA
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23
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Diaz LI, Mony S, Klapman J. Narrative review of the role of gastroenterologist in the diagnosis, treatment and palliation in gastric and gastroesophageal cancer. ANNALS OF TRANSLATIONAL MEDICINE 2020; 8:1106. [PMID: 33145325 PMCID: PMC7575985 DOI: 10.21037/atm-20-4143] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Esophageal cancer (EC) and gastric cancer (GC) carry a high mortality rate. Unfortunately, a majority of patients are asymptomatic and at the time of diagnosis, the disease may invariably be in its advanced stages with limited curative options. Thus, it is imperative to recognize certain risk factors including gastroesophageal reflux disease (GERD), male gender, pre-existing Barrett’s esophagus, smoking history, obesity, Helicobacter pylori infection, atrophic gastritis among others for both EC and GC, intervene on time with screening and surveillance modalities if indicated and optimize treatment plans. With advances in endoscopic techniques, early neoplastic lesions are increasingly managed by gastroenterologists, offering an alternative to surgery. The gold standard for diagnosis of EC and GC is high definition endoscopy with adequate targeted biopsies. Endoscopic ultrasound (EUS) is a key in the staging of early cancers dictating the pathway for treatment options. We also play a key role in palliation cases with the aim to reduce the symptoms like nausea, vomiting and even when possible, restore oral intake and improve nutrition in both advanced GC and EC. This review article discusses the risk factors, diagnostic and endoscopic treatment modalities of early EC and GC and palliation of advanced cancer where gastroenterologists play a key role.
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Affiliation(s)
- Liege I Diaz
- Department of Endoscopic Oncology, Moffitt Cancer Center, Tampa, FL, USA
| | - Shruti Mony
- Division of Digestive Diseases and Nutrition, University of South Florida, Tampa, FL, USA
| | - Jason Klapman
- Department of Endoscopic Oncology, Moffitt Cancer Center, Tampa, FL, USA
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24
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Maitra I, Date RS, Martin FL. Towards screening Barrett's oesophagus: current guidelines, imaging modalities and future developments. Clin J Gastroenterol 2020; 13:635-649. [PMID: 32495144 PMCID: PMC7519897 DOI: 10.1007/s12328-020-01135-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2020] [Accepted: 05/21/2020] [Indexed: 02/07/2023]
Abstract
Barrett's oesophagus is the only known precursor to oesophageal adenocarcinoma (OAC). Although guidelines on the screening and surveillance exist in Barrett's oesophagus, the current strategies are inadequate. Oesophagogastroduodenoscopy (OGD) is the gold standard method in screening for Barrett's oesophagus. This invasive method is expensive with associated risks negating its use as a current screening tool for Barrett's oesophagus. This review explores current definitions, epidemiology, biomarkers, surveillance, and screening in Barrett's oesophagus. Imaging modalities applicable to this condition are discussed, in addition to future developments. There is an urgent need for an alternative non-invasive method of screening and/or surveillance which could be highly beneficial towards reducing waiting times, alleviating patient fears and reducing future costs in current healthcare services. Vibrational spectroscopy has been shown to be promising in categorising Barrett's oesophagus through to high-grade dysplasia (HGD) and OAC. These techniques need further validation through multicentre trials.
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Affiliation(s)
- Ishaan Maitra
- School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Preston, PR1 2HE UK
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25
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Bennett C, Green S, DeCaestecker J, Almond M, Barr H, Bhandari P, Ragunath K, Singh R, Jankowski J. Surgery versus radical endotherapies for early cancer and high-grade dysplasia in Barrett's oesophagus. Cochrane Database Syst Rev 2020; 5:CD007334. [PMID: 32442322 PMCID: PMC7390331 DOI: 10.1002/14651858.cd007334.pub5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND Barrett's oesophagus is one of the most common pre-malignant lesions in the world. Currently the mainstay of therapy is surgical management of advanced cancer but this has improved the five-year survival very little since the 1980s. As a consequence, improved survival relies on early detection through endoscopic surveillance programmes. Success of this strategy relies on the fact that late-stage pre-malignant lesions or very early cancers can be cured by intervention. Currently there is considerable controversy over which method is best: that is conventional open surgery or endotherapy (techniques involving endoscopy). OBJECTIVES We used data from randomised controlled trials (RCTs) to examine the effectiveness of endotherapies compared with surgery in people with Barrett's oesophagus, those with early neoplasias (defined as high-grade dysplasia (HGD) and those with early cancer (defined as carcinoma in-situ, superficially invasive, early cancer or superficial cancer T-1m (T1-a) and T-1sm (T1-b)). SEARCH METHODS We used the Cochrane highly sensitive search strategy to identify RCTs in MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), ISI Web of Science, EBMR, Controlled Trials mRCT and ISRCTN, and LILACS, in July and August 2008. The searches were updated in 2009 and again in April 2012. SELECTION CRITERIA Types of studies: RCTs comparing endotherapies with surgery in the treatment of high-grade dysplasia or early cancer. All cellular types of cancer were included (i.e. adenocarcinomas, squamous cell carcinomas and more unusual types) but will be discussed separately. TYPES OF PARTICIPANTS patients of any age and either gender with a histologically confirmed diagnosis of early neoplasia (HGD and early cancer) in Barrett's or squamous lined oesophagus. Types of interventions; endotherapies (the intervention) compared with surgery (the control), all with curative intent. DATA COLLECTION AND ANALYSIS Reports of studies that meet the inclusion criteria for this review would have been analysed using the methods detailed in Appendix 9. MAIN RESULTS We did not identify any studies that met the inclusion criteria. In total we excluded 13 studies that were not RCTs but that compared surgery and endotherapies. AUTHORS' CONCLUSIONS This Cochrane review has indicated that there are no RCTs to compare management options in this vital area, therefore trials should be undertaken as a matter of urgency. The problems with such randomised methods are standardising surgery and endotherapies in all sites, standardising histopathology in all centres, assessing which patients are fit or unfit for surgery and making sure there are relevant outcomes for the study (i.e. long-term survival (over five or more years)) and no progression of HGD.
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Affiliation(s)
- Cathy Bennett
- Centre for Innovative Research Across the Life Course (CIRAL), Coventry University, Coventry, UK
| | - Susi Green
- Gastroenterology, Portsmouth Hospitals Trust, Cosham, UK
| | | | - Max Almond
- Department of Oesphogastric Surgery, Gloucestershire Royal Hospital, Gloucester, UK
| | - Hugh Barr
- Surgery, Gloucester Royal Hospital, Gloucester, UK
| | - Pradeep Bhandari
- Gastroenterology, Portsmouth Hospitals NHS Trust, Portsmouth, UK
| | - Krish Ragunath
- Wolfson Digestive Diseases Centre, Queens Medical Centre, Nottingham University NHS Trust, Nottingham, UK
| | - Rajvinder Singh
- Gastroenterology, The Lyell McEwin Hospital, Elizabeth Vale, Australia
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Hamel C, Ahmadzai N, Beck A, Thuku M, Skidmore B, Pussegoda K, Bjerre L, Chatterjee A, Dennis K, Ferri L, Maziak DE, Shea BJ, Hutton B, Little J, Moher D, Stevens A. Screening for esophageal adenocarcinoma and precancerous conditions (dysplasia and Barrett's esophagus) in patients with chronic gastroesophageal reflux disease with or without other risk factors: two systematic reviews and one overview of reviews to inform a guideline of the Canadian Task Force on Preventive Health Care (CTFPHC). Syst Rev 2020; 9:20. [PMID: 31996261 PMCID: PMC6990541 DOI: 10.1186/s13643-020-1275-2] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2019] [Accepted: 01/07/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Two reviews and an overview were produced for the Canadian Task Force on Preventive Health Care guideline on screening for esophageal adenocarcinoma in patients with chronic gastroesophageal reflux disease (GERD) without alarm symptoms. The goal was to systematically review three key questions (KQs): (1) The effectiveness of screening for these conditions; (2) How adults with chronic GERD weigh the benefits and harms of screening, and what factors contribute to their preferences and decision to undergo screening; and (3) Treatment options for Barrett's esophagus (BE), dysplasia or stage 1 EAC (overview of reviews). METHODS Bibliographic databases (e.g. Ovid MEDLINE®) were searched for each review in October 2018. We also searched for unpublished literature (e.g. relevant websites). The liberal accelerated approach was used for title and abstract screening. Two reviewers independently screened full-text articles. Data extraction and risk of bias assessments were completed by one reviewer and verified by another reviewer (KQ1 and 2). Quality assessments were completed by two reviewers independently in duplicate (KQ3). Disagreements were resolved through discussion. We used various risk of bias tools suitable for study design. The GRADE framework was used for rating the certainty of the evidence. RESULTS Ten studies evaluated the effectiveness of screening. One retrospective study reported no difference in long-term survival (approximately 6 to 12 years) between those who had a prior esophagogastroduodenoscopy and those who had not (adjusted HR 0.93, 95% confidence interval (CI) 0.58-1.50). Though there may be higher odds of a stage 1 diagnosis than a more advanced diagnosis (stage 2-4) if an EGD had been performed in the previous 5 years (OR 2.27, 95% CI 1.00-7.67). Seven studies compared different screening modalities, and showed little difference between modalities. Three studies reported on patients' unwillingness to be screened (e.g. due to anxiety, fear of gagging). Eleven systematic reviews evaluated treatment modalities, providing some evidence of early treatment effect for some outcomes. CONCLUSIONS Little evidence exists on the effectiveness of screening and values and preferences to screening. Many treatment modalities have been evaluated, but studies are small. Overall, there is uncertainty in understanding the effectiveness of screening and early treatments. SYSTEMATIC REVIEW REGISTRATIONS PROSPERO (CRD42017049993 [KQ1], CRD42017050014 [KQ2], CRD42018084825 [KQ3]).
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Affiliation(s)
- Candyce Hamel
- Ottawa Hospital Research Institute, Knowledge Synthesis Group, 501 Smyth Road, Ottawa, ON, Canada.
| | - Nadera Ahmadzai
- Ottawa Hospital Research Institute, Knowledge Synthesis Group, 501 Smyth Road, Ottawa, ON, Canada
| | - Andrew Beck
- Ottawa Hospital Research Institute, Knowledge Synthesis Group, 501 Smyth Road, Ottawa, ON, Canada
| | - Micere Thuku
- Ottawa Hospital Research Institute, Knowledge Synthesis Group, 501 Smyth Road, Ottawa, ON, Canada
| | - Becky Skidmore
- Ottawa Hospital Research Institute, Knowledge Synthesis Group, 501 Smyth Road, Ottawa, ON, Canada
| | - Kusala Pussegoda
- Ottawa Hospital Research Institute, Knowledge Synthesis Group, 501 Smyth Road, Ottawa, ON, Canada
| | - Lise Bjerre
- Department of Family Medicine, University of Ottawa, Ottawa, ON, Canada
| | - Avijit Chatterjee
- Gastroenterology Department, Faculty of Medicine, Unveristy of Ottawa, Ottawa, ON, Canada
| | - Kristopher Dennis
- Ottawa Hospital Research Institute, Cancer Therapeutics Program, Ottawa, ON, Canada
| | - Lorenzo Ferri
- Division of Thoracic and Upper Gastrointestinal Surgery, McGill University, Montreal, QC, Canada
| | - Donna E Maziak
- Department of Surgery and The Ottawa Hospital, Department of Thoracic Surgery, University of Ottawa, Ottawa, ON, Canada
| | - Beverley J Shea
- Ottawa Hospital Research Institute, Knowledge Synthesis Group, 501 Smyth Road, Ottawa, ON, Canada
| | - Brian Hutton
- Ottawa Hospital Research Institute, Knowledge Synthesis Group, 501 Smyth Road, Ottawa, ON, Canada.,School of Epidemiology and Public Health, University of Ottawa, Ottawa, ON, Canada
| | - Julian Little
- School of Epidemiology and Public Health, University of Ottawa, Ottawa, ON, Canada
| | - David Moher
- Ottawa Hospital Research Institute, Knowledge Synthesis Group, 501 Smyth Road, Ottawa, ON, Canada.,School of Epidemiology and Public Health, University of Ottawa, Ottawa, ON, Canada
| | - Adrienne Stevens
- Ottawa Hospital Research Institute, Knowledge Synthesis Group, 501 Smyth Road, Ottawa, ON, Canada
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28
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Wilson BC, Weersink RA. The Yin and Yang of PDT and PTT. Photochem Photobiol 2019; 96:219-231. [PMID: 31769516 DOI: 10.1111/php.13184] [Citation(s) in RCA: 41] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2019] [Accepted: 10/24/2019] [Indexed: 12/16/2022]
Abstract
In Chinese philosophy, yin and yang ("dark-bright," "negative-positive") describe how seemingly opposite or contrary forces may actually be complementary, interconnected and interdependent. This paper provides this perspective on photodynamic and photothermal therapies, with a focus on the treatment of solid tumors. The relative strengths and weaknesses of each modality, both current and emerging, are considered with respect to the underlying biophysics, the required technologies, the biological effects, their translation into clinical practice and the realized or potential clinical outcomes. For each specific clinical application, one or the other modality may be clearly preferred, or both are effectively equivalent in terms of the various scientific/technological/practical/clinical trade-offs involved. Alternatively, a combination may the best approach. Such combined approaches may be facilitated by the use of multifunctional nanoparticles. It is important to understand the many factors that go into the selection of the optimal approach and the objective of this paper is to provide guidance on this.
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Affiliation(s)
- Brian C Wilson
- Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada
| | - Robert A Weersink
- University Health Network/University of Toronto, Toronto, ON, M5G 1L7, Canada
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29
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Ahmed O, Ajani JA, Lee JH. Endoscopic management of esophageal cancer. World J Gastrointest Oncol 2019; 11:830-841. [PMID: 31662822 PMCID: PMC6815921 DOI: 10.4251/wjgo.v11.i10.830] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2019] [Revised: 05/29/2019] [Accepted: 08/28/2019] [Indexed: 02/05/2023] Open
Abstract
Esophageal cancer (EC) generally consists of squamous cell carcinoma (which arise from squamous epithelium) and adenocarcinoma (which arise from columnar epithelium). Due to the increased recognition of risk factors associated with EC and the development of screening programs, there has been an increase in the diagnosis of early EC. Early EC is amenable to curative therapy by endoscopy, which can be performed by either endoscopic resection or endoscopic ablation. Endoscopic resection consists of either endoscopic mucosal resection (preferred in cases of adenocarcinoma) or endoscopic submucosal dissection (preferred in cases of squamous cell carcinoma). Endoscopic ablation can be performed by either radiofrequency ablation, cryotherapy, argon plasma coagulation or photodynamic therapy, amongst others. Endoscopy can also assist in the management of complications post-esophageal surgery, such as anastomotic leaks and perforations. Finally, there is a growing role for endoscopy to manage end-of-life palliative symptoms, especially dysphagia. The growing use of esophageal stents, debulking therapy and dilation can assist in improving a patient’s quality of life. In this review, we examine the multiple roles of endoscopy in the management of patients with EC.
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Affiliation(s)
- Osman Ahmed
- Department of Gastroenterology, Hepatology and Nutrition, University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
| | - Jaffer A Ajani
- Department of Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
| | - Jeffrey H Lee
- Department of Gastroenterology, Hepatology and Nutrition, University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
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30
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Wu H, Minamide T, Yano T. Role of photodynamic therapy in the treatment of esophageal cancer. Dig Endosc 2019; 31:508-516. [PMID: 30667112 DOI: 10.1111/den.13353] [Citation(s) in RCA: 65] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2018] [Accepted: 01/17/2019] [Indexed: 12/13/2022]
Abstract
Photodynamic therapy (PDT), a treatment of choice for cancer, induces a photochemical reaction, thereby eradicating tumor cells. This is achieved through the administration of a photosensitizer drug, which is activated with a laser after localization to the tumor mass, and is an approved curative endoscopic ablative treatment for superficial esophageal squamous cell carcinoma (ESCC) in Japan. PDT has been approved for dysplastic Barrett's esophagus and as a palliative treatment for patients with symptomatic obstructive esophageal cancer in US. However, its adverse events and complicated procedure and the development of alternative endoscopic procedures such as endoscopic submucosal dissection, radiofrequency ablation and cryotherapy, have largely limited the practice of PDT in esophageal cancer worldwide. Recently, owing to the invention of second-generation PDT using talaporfin sodium and diode laser, PDT can be performed with less phototoxicity and therefore has regained popularity in the treatment of ESCC. As a salvage treatment for patients with local failure after chemoradiotherapy (CRT), PDT has shown promising complete response with less phototoxicity and shorter sun shade period. In addition, the efficacy and safety of PDT in patients with local failure of ESCC after CRT were shown in several clinical trials. The direction of the study interest of the next-generation PDT is the safety and potential expansion of the indications for its application in the future. This review covers the PDT for the treatment of ESCC and dysplastic Barrett's esophagus, with special focus on the role of PDT in practice for esophageal cancer.
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Affiliation(s)
- Hao Wu
- Department of Gastroenterology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.,Department of Gastroenterology and Endoscopy, National Cancer Center Hospital East, Chiba, Japan
| | - Tatsunori Minamide
- Department of Gastroenterology and Endoscopy, National Cancer Center Hospital East, Chiba, Japan
| | - Tomonori Yano
- Department of Gastroenterology and Endoscopy, National Cancer Center Hospital East, Chiba, Japan
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31
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Mohan BP, Krishnamoorthi R, Ponnada S, Shakhatreh M, Jayaraj M, Garg R, Law J, Larsen M, Irani S, Ross A, Adler DG. Liquid Nitrogen Spray Cryotherapy in Treatment of Barrett's Esophagus, where do we stand? A Systematic Review and Meta-Analysis. Dis Esophagus 2019; 32:5304729. [PMID: 30715267 DOI: 10.1093/dote/doy130] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2018] [Revised: 12/06/2018] [Indexed: 12/11/2022]
Abstract
Radiofrequency ablation (RFA) is the preferred treatment option for Barrett's esophagus (BE) to achieve complete eradication (CE) of dysplasia (D), and intestinal metaplasia (IM). Cryotherapy, using liquid nitrogen (LNC), is a cold-induced tissue-injury technique option for the ablation of BE. We conducted a systematic review and meta-analysis to assess the overall efficacy and safety of LNC in the treatment of BE. We conducted a search of multiple electronic databases and conference proceedings from inception through June 2018. The primary outcome was to estimate the pooled rates of CE-IM, CE-D, and CE-HGD. The secondary outcome was to estimate the risk of adverse events and recurrence of disease after LNC. Nine studies reported 386 patients who were treated with LNC. The pooled rate of CE-IM was 56.5% (95% CI 48.5-64.2, I2 = 47), pooled rate of CE-D was 83.5% (95% CI 78.3-87.7, I2 = 22.8), and pooled rate of CE-HGD was 86.5% (95% CI 64.4-95.8, I2 = 88.1). Rate of adverse events was 4.7%, and the risk of BE recurrence was 12.7%. On subgroup analysis, the pooled rate of CE-IM with LNC in patients who failed RFA was 58.4% (95% CI 47.2-68.8, I2 = 32.5), and the pooled rate of CE-D in the same population was 81.9% (95% CI 72.5-88.6, I2 = 5.9). CE-D rates with LNC are comparable to RFA while CE-IM rates appear to be lower than the rates achievable with RFA. CE-IM rate in RFA failed patients is 58.4% and thus LNC is a rescue option to consider in this population.
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Affiliation(s)
- B P Mohan
- DCH Medical Center, University of Alabama, Tuscaloosa, Alabama
| | - R Krishnamoorthi
- Digestive Diseases Institute, Virginia Mason Medical Center, Seattle, Washington
| | - S Ponnada
- Carilion Roanoke Memorial Hospital, Roanoke, Virginia
| | - M Shakhatreh
- Rapides Regional Medical Center, Alexandria, Louisiana
| | - M Jayaraj
- University of Nevada, Las Vegas, Nevada
| | - R Garg
- Cleveland Clinic Foundation, Cleveland, Ohio
| | - J Law
- Digestive Diseases Institute, Virginia Mason Medical Center, Seattle, Washington
| | - M Larsen
- Digestive Diseases Institute, Virginia Mason Medical Center, Seattle, Washington
| | - S Irani
- Digestive Diseases Institute, Virginia Mason Medical Center, Seattle, Washington
| | - A Ross
- Digestive Diseases Institute, Virginia Mason Medical Center, Seattle, Washington
| | - D G Adler
- Division of Gastroenterology and Hepatology, University of Utah School of Medicine, Salt Lake City, Utah, USA
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Yassine AA, Lilge L, Betz V. Optimizing interstitial photodynamic therapy with custom cylindrical diffusers. JOURNAL OF BIOPHOTONICS 2019; 12:e201800153. [PMID: 30178604 DOI: 10.1002/jbio.201800153] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/27/2018] [Accepted: 09/02/2018] [Indexed: 05/07/2023]
Abstract
Interstitial photodynamic therapy (iPDT) has shown promise recently as a minimally invasive cancer treatment, partially due to the development of non-toxic photosensitizers in the absence of activation light. However, a major challenge in iPDT is the pre-treatment planning process that specifies the number of diffusers needed, along with their positions and allocated powers, to confine the light distribution to the target volume as much as possible. In this work, a new power allocation algorithm for cylindrical light diffusers including those that can produce customized longitudinal (tailored) emission profiles is introduced. The proposed formulation is convex to guarantee the minimum over-dose possible on the surrounding organs-at-risk. The impact of varying the diffuser lengths and penetration angles on the quality of the plan is evaluated. The results of this study are demonstrated for different photosensitizers activated at different wavelengths and simulated on virtual tumors modeling virtual glioblastoma multiforme cases. Results show that manufacturable cylindrical diffusers with tailored emission profiles can significantly outperform those with conventional flat profiles with an average damage reduction on white matter of 15% to 55% and on gray matter of 23% to 58%.
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Affiliation(s)
- Abdul-Amir Yassine
- Edward S. Rogers Sr. Department of Electrical and Computer Engineering, University of Toronto, Toronto, Canada
| | - Lothar Lilge
- Princess Margaret Cancer Centre, Toronto Medical Discovery Tower, Toronto, Canada
- Department of Medical Biophysics, University of Toronto, Toronto, Canada
| | - Vaughn Betz
- Edward S. Rogers Sr. Department of Electrical and Computer Engineering, University of Toronto, Toronto, Canada
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Pecere S, Costamagna G. Endoscopic therapy for confirmed low-grade dysplasia in Barrett's esophagus. Transl Gastroenterol Hepatol 2018; 3:83. [PMID: 30505970 DOI: 10.21037/tgh.2018.10.01] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2018] [Accepted: 09/28/2018] [Indexed: 12/24/2022] Open
Abstract
Barrett's esophagus (BE) is a premalignant condition characterized by replacement of the esophageal lining with metastatic columnar epithelium. To date, the management in case of confirmed low-grade dysplasia (LGD) remains controversial. In this article we summarize the available endoscopic options and their results in terms of efficacy and safety in the treatment of confirmed LGD in BE.
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Affiliation(s)
- Silvia Pecere
- Unità Operativa Complessa di Endoscopia Digestiva Chirurgica, Dipartimento Scienze Gastroenterologiche, Endocrino-Metaboliche e Nefro-Urologiche Istituto di Clinica Chirurgica Generale e Terapia Chirurgica Fondazione Policlinico Universitario A. Gemelli, Università Cattolica del Sacro Cuore, Roma, Italia
| | - Guido Costamagna
- Unità Operativa Complessa di Endoscopia Digestiva Chirurgica, Dipartimento Scienze Gastroenterologiche, Endocrino-Metaboliche e Nefro-Urologiche Istituto di Clinica Chirurgica Generale e Terapia Chirurgica Fondazione Policlinico Universitario A. Gemelli, Università Cattolica del Sacro Cuore, Roma, Italia
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Singh T, Sanaka MR, Thota PN. Endoscopic therapy for Barrett’s esophagus and early esophageal cancer: Where do we go from here? World J Gastrointest Endosc 2018; 10:165-174. [PMID: 30283599 PMCID: PMC6162248 DOI: 10.4253/wjge.v10.i9.165] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2018] [Revised: 06/13/2018] [Accepted: 06/28/2018] [Indexed: 02/06/2023] Open
Abstract
Since Barrett’s esophagus is a precancerous condition, efforts have been made for its eradication by various ablative techniques. Initially, laser ablation was attempted in non-dysplastic Barrett’s esophagus and subsequently, endoscopic ablation using photodynamic therapy was used in Barrett’s patients with high-grade dysplasia who were poor surgical candidates. Since then, various ablative therapies have been developed with radiofrequency ablation having the best quality of evidence. Resection of dysplastic areas only without complete removal of entire Barrett’s segment is associated with high risk of developing metachronous neoplasia. Hence, the current standard of management for Barrett’s esophagus includes endoscopic mucosal resection of visible abnormalities followed by ablation to eradicate remaining Barrett’s epithelium. Although endoscopic therapy cannot address regional lymph node metastases, such nodal involvement is present in only 1% to 2% of patients with intramucosal adenocarcinoma in Barrett esophagus and therefore is useful in intramucosal cancers. Post ablation surveillance is recommended as recurrence of intestinal metaplasia and dysplasia have been reported. This review includes a discussion of the technique, efficacy and complication rate of currently available ablation techniques such as radiofrequency ablation, cryotherapy, argon plasma coagulation and photodynamic therapy as well as endoscopic mucosal resection. A brief discussion of the emerging technique, endoscopic submucosal dissection is also included.
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Affiliation(s)
- Tavankit Singh
- Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH 44195, United States
| | - Madhusudhan R Sanaka
- Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH 44195, United States
| | - Prashanthi N Thota
- Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH 44195, United States
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Kohoutova D, Haidry R, Banks M, Butt MA, Dunn J, Thorpe S, Lovat L. Long-term outcomes of the randomized controlled trial comparing 5-aminolaevulinic acid and Photofrin photodynamic therapy for Barrett's oesophagus related neoplasia. Scand J Gastroenterol 2018; 53:527-532. [PMID: 29161901 DOI: 10.1080/00365521.2017.1403646] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE Photodynamic therapy (PDT) was used as therapy for early neoplasia associated with Barrett's oesophagus (BE). This is 5-year follow-up of patients enrolled into randomised controlled trial of 5-aminolaevulinic acid (ALA) vs. Photofrin PDT. METHODS Biopsies were taken from original Barrett's segment during endoscopic follow up using Seattle protocol. Endoscopic mucosal resection (EMR) ± radiofrequency ablation (RFA) was preferred therapy in patients who failed PDT and/or had recurrent neoplasia. RESULTS Fifty eight of 64 patients enrolled in the original trial were followed up including 31 patients treated with ALA PDT (17 patients with ≤6 cm, 14 patients with >6 cm segment of BE) and 27 treated with Photofrin PDT (14 patients with ≤6 cm, 13 patients with >6 cm BE). Initial success was achieved in 65% (20/31) ALA and 48% (13/27) Photofrin patients (p = .289). Thirty five percent patients (7/20) relapsed in ALA group and 54% (7/13) relapsed in Photofrin group (p = .472). At a median follow-up of 67 months, no significant difference was found in long-term complete reversal of intestinal metaplasia (CR-IM) and complete reversal of dysplasia (CR-D) between ALA and Photofrin groups (78% vs. 63%; p = .18; 90% vs. 76%; p = .26). Original length of BE did not alter long-term outcome. Four patients from each group progressed to invasive oesophageal adenocarcinoma. Initial success of ALA PDT was associated with significantly better likelihood of long-term remission (p = .03). CONCLUSIONS Initial response to PDT plays key role in long term outcome. RFA ± EMR have, however, become preferred minimally invasive ablative therapy for BE-related neoplasia due to poor efficacy of PDT.
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Affiliation(s)
- Darina Kohoutova
- a Division of Surgery & Interventional Science , University College London , London , UK.,b Division of GI Services , University College London Hospital , London , UK
| | - Rehan Haidry
- a Division of Surgery & Interventional Science , University College London , London , UK.,b Division of GI Services , University College London Hospital , London , UK
| | - Matthew Banks
- a Division of Surgery & Interventional Science , University College London , London , UK.,b Division of GI Services , University College London Hospital , London , UK
| | - Mohammed Adil Butt
- a Division of Surgery & Interventional Science , University College London , London , UK.,b Division of GI Services , University College London Hospital , London , UK
| | - Jason Dunn
- c Guy's and St Thomas' NHS Foundation Trust , London , UK
| | - Sally Thorpe
- b Division of GI Services , University College London Hospital , London , UK
| | - Laurence Lovat
- a Division of Surgery & Interventional Science , University College London , London , UK.,b Division of GI Services , University College London Hospital , London , UK
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37
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Pye H, Butt MA, Funnell L, Reinert HW, Puccio I, Rehman Khan SU, Saouros S, Marklew JS, Stamati I, Qurashi M, Haidry R, Sehgal V, Oukrif D, Gandy M, Whitaker HC, Rodriguez-Justo M, Novelli M, Hamoudi R, Yahioglu G, Deonarain MP, Lovat LB. Using antibody directed phototherapy to target oesophageal adenocarcinoma with heterogeneous HER2 expression. Oncotarget 2018; 9:22945-22959. [PMID: 29796164 PMCID: PMC5955430 DOI: 10.18632/oncotarget.25159] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2018] [Accepted: 03/28/2018] [Indexed: 12/22/2022] Open
Abstract
Early oesophageal adenocarcinoma (OA) and pre-neoplastic dysplasia may be treated with endoscopic resection and ablative techniques such as photodynamic therapy (PDT). Though effective, discrete areas of disease may be missed leading to recurrence. PDT further suffers from the side effects of off-target photosensitivity. A tumour specific and light targeted therapeutic agent with optimised pharmacokinetics could be used to destroy residual cancerous cells left behind after resection. A small molecule antibody-photosensitizer conjugate was developed targeting human epidermal growth factor receptor 2 (HER2). This was tested in an in vivo mouse model of human OA using a xenograft flank model with clinically relevant low level HER2 expression and heterogeneity. In vitro we demonstrate selective binding of the conjugate to tumour versus normal tissue. Light dependent cytotoxicity of the phototherapy agent in vitro was observed. In an in vivo OA mouse xenograft model the phototherapy agent had desirable pharmacokinetic properties for tumour uptake and blood clearance time. PDT treatment caused tumour growth arrest in all the tumours despite the tumours having a clinically defined low/negative HER2 expression level. This new phototherapy agent shows therapeutic potential for treatment of both HER2 positive and borderline/negative OA.
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Affiliation(s)
- Hayley Pye
- Department for Tissue and Energy, Division of Surgery and Interventional Science, University College London, London, UK
| | - Mohammed Adil Butt
- Department for Tissue and Energy, Division of Surgery and Interventional Science, University College London, London, UK.,Upper Gastrointestinal Service, University College London Hospitals NHS Foundation Trust, London, UK
| | - Laura Funnell
- Department for Tissue and Energy, Division of Surgery and Interventional Science, University College London, London, UK
| | - Halla W Reinert
- Department for Tissue and Energy, Division of Surgery and Interventional Science, University College London, London, UK
| | - Ignazio Puccio
- Department for Tissue and Energy, Division of Surgery and Interventional Science, University College London, London, UK
| | - Saif U Rehman Khan
- Department for Tissue and Energy, Division of Surgery and Interventional Science, University College London, London, UK
| | - Savvas Saouros
- Antikor BioPharma, Stevenage, UK.,Imperial College London, London, UK
| | | | | | - Maryam Qurashi
- Department for Tissue and Energy, Division of Surgery and Interventional Science, University College London, London, UK.,Imperial College London, London, UK
| | - Rehan Haidry
- Upper Gastrointestinal Service, University College London Hospitals NHS Foundation Trust, London, UK
| | - Vinay Sehgal
- Department for Tissue and Energy, Division of Surgery and Interventional Science, University College London, London, UK.,Upper Gastrointestinal Service, University College London Hospitals NHS Foundation Trust, London, UK
| | - Dahmane Oukrif
- Department of Pathology, University College London, London, UK
| | - Michael Gandy
- Department for Tissue and Energy, Division of Surgery and Interventional Science, University College London, London, UK
| | - Hayley C Whitaker
- Department for Tissue and Energy, Division of Surgery and Interventional Science, University College London, London, UK
| | | | - Marco Novelli
- Department of Pathology, University College London, London, UK
| | - Rifat Hamoudi
- Department for Tissue and Energy, Division of Surgery and Interventional Science, University College London, London, UK.,Sharjah Institute for Medical Research, College of Medicine, University of Sharjah, Sharjah, UAE
| | - Gokhan Yahioglu
- Antikor BioPharma, Stevenage, UK.,Imperial College London, London, UK
| | - Mahendra P Deonarain
- Department for Tissue and Energy, Division of Surgery and Interventional Science, University College London, London, UK.,Antikor BioPharma, Stevenage, UK.,Imperial College London, London, UK
| | - Laurence B Lovat
- Department for Tissue and Energy, Division of Surgery and Interventional Science, University College London, London, UK.,Upper Gastrointestinal Service, University College London Hospitals NHS Foundation Trust, London, UK
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Yassine AA, Kingsford W, Xu Y, Cassidy J, Lilge L, Betz V. Automatic interstitial photodynamic therapy planning via convex optimization. BIOMEDICAL OPTICS EXPRESS 2018; 9:898-920. [PMID: 29552420 PMCID: PMC5854086 DOI: 10.1364/boe.9.000898] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/25/2017] [Revised: 01/15/2018] [Accepted: 01/16/2018] [Indexed: 05/23/2023]
Abstract
Finding a high-quality treatment plan is an essential, yet difficult, stage of Photodynamic therapy (PDT) as it will determine the therapeutic efficacy in eradicating malignant tumors. A high-quality plan is patient-specific, and provides clinicians with the number of fiber-based spherical diffusers, their powers, and their interstitial locations to deliver the required light dose to destroy the tumor while minimizing the damage to surrounding healthy tissues. In this work, we propose a general convex light source power allocation algorithm that, given light source locations, guarantees optimality of the resulting solution in minimizing the over/under-dosage of volumes of interest. Furthermore, we provide an efficient framework for source selection with concomitant power reallocation to achieve treatment plans with a clinically feasible number of sources and comparable quality. We demonstrate our algorithms on virtual test cases that model glioblastoma multiforme tumors, and evaluate the performance of four different photosensitizers with different activation wavelengths and specific tissue uptake ratios. Results show an average reduction of the damage to organs-at-risk (OAR) by 29% to 31% with comparable runtime to existing power allocation techniques.
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Affiliation(s)
- Abdul-Amir Yassine
- Edward S. Rogers Sr. Department of Electrical and Computer Engineering, University of Toronto, 10 King's College Rd, Toronto, ON M5S3G8, Canada
| | - William Kingsford
- Division of Engineering Science, University of Toronto, 27 King's College Circle, Toronto, ON M5S1A1, Canada
| | - Yiwen Xu
- Department of Mathematics, University of British Columbia, 1980 Mathematics Road, Vancouver, BC V6T1Z2, Canada
| | - Jeffrey Cassidy
- Edward S. Rogers Sr. Department of Electrical and Computer Engineering, University of Toronto, 10 King's College Rd, Toronto, ON M5S3G8, Canada
| | - Lothar Lilge
- Princess Margaret Cancer Centre, Toronto Medical Discovery Tower, 101 College Street, Toronto, ON M5G1L7, Canada
| | - Vaughn Betz
- Edward S. Rogers Sr. Department of Electrical and Computer Engineering, University of Toronto, 10 King's College Rd, Toronto, ON M5S3G8, Canada
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Raghu Subramanian C, Triadafilopoulos G. Diagnosis and therapy of esophageal squamous cell dysplasia and early esophageal squamous cell cancer. Gastroenterol Rep (Oxf) 2017. [DOI: 10.1093/gastro/gox022] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
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Hartmans E, Linssen MD, Sikkens C, Levens A, Witjes MJ, van Dam GM, Nagengast WB. Tyrosine kinase inhibitor induced growth factor receptor upregulation enhances the efficacy of near-infrared targeted photodynamic therapy in esophageal adenocarcinoma cell lines. Oncotarget 2017; 8:29846-29856. [PMID: 28415738 PMCID: PMC5444708 DOI: 10.18632/oncotarget.16165] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2016] [Accepted: 02/27/2017] [Indexed: 12/12/2022] Open
Abstract
Esophageal carcinoma (EC) is a global health problem, with disappointing 5-year survival rates of only 15-25%. Near-infrared targeted photodynamic therapy (NIR-tPDT) is a novel strategy in which cancer-targeted phototoxicity is able to selectively treat malignant cells. In this in vitro report we demonstrate the applicability of antibody-based NIR-tPDT in esophageal adenocarcinoma (EAC), using the phototoxic compounds cetuximab-IRDye700DX and trastuzumab-IRDye700DX, targeting respectively epidermal growth factor receptor 1 (EGFR) and 2 (HER2). Furthermore, we demonstrate that NIR-tPDT can be made more effective by tyrosine kinase inhibitor (TKI) induced growth receptor upregulation. Together, these results unveil a novel strategy for non-invasive EAC treatment, and by pretreatment-induced receptor upregulation its future clinical application may be optimized.
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Affiliation(s)
- Elmire Hartmans
- Department of Gastroenterology and Hepatology, University of Groningen, University Medical Centre, Groningen, The Netherlands
| | - Matthijs D. Linssen
- Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Centre, Groningen, The Netherlands
| | - Claire Sikkens
- Department of Gastroenterology and Hepatology, University of Groningen, University Medical Centre, Groningen, The Netherlands
| | - Afra Levens
- Department of Gastroenterology and Hepatology, University of Groningen, University Medical Centre, Groningen, The Netherlands
| | - Max J.H. Witjes
- Department of Oral and Maxillofacial Surgery, University of Groningen, University Medical Centre, Groningen, The Netherlands
| | - Gooitzen M. van Dam
- Department of Surgery, Nuclear Medicine and Molecular imaging and Intensive Care, University of Groningen, University Medical Centre, Groningen, The Netherlands
| | - Wouter B. Nagengast
- Department of Gastroenterology and Hepatology, University of Groningen, University Medical Centre, Groningen, The Netherlands
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41
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Eluri S, Shaheen NJ. Barrett's esophagus: diagnosis and management. Gastrointest Endosc 2017; 85:889-903. [PMID: 28109913 PMCID: PMC5392444 DOI: 10.1016/j.gie.2017.01.007] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2016] [Accepted: 01/07/2017] [Indexed: 02/08/2023]
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Butt MA, Pye H, Haidry RJ, Oukrif D, Khan SUR, Puccio I, Gandy M, Reinert HW, Bloom E, Rashid M, Yahioglu G, Deonarain MP, Hamoudi R, Rodriguez-Justo M, Novelli MR, Lovat LB. Upregulation of mucin glycoprotein MUC1 in the progression to esophageal adenocarcinoma and therapeutic potential with a targeted photoactive antibody-drug conjugate. Oncotarget 2017; 8:25080-25096. [PMID: 28212575 PMCID: PMC5421911 DOI: 10.18632/oncotarget.15340] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2016] [Accepted: 01/24/2017] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND Mucin glycoprotein 1 (MUC1) is a glycosylated transmembrane protein on epithelial cells. We investigate MUC1 as a therapeutic target in Barrett's epithelium (BE) and esophageal adenocarcinoma (EA) and provide proof of concept for a light based therapy targeting MUC1. RESULTS MUC1 was present in 21% and 30% of significantly enriched pathways comparing BE and EA to squamous epithelium respectively. MUC1 gene expression was x2.3 and x2.2 higher in BE (p=<0.001) and EA (p=0.03). MUC1 immunohistochemical expression increased during progression to EA and followed tumor invasion. HuHMFG1 based photosensitive antibody drug conjugates (ADC) showed cell internalization, MUC1 selective and light-dependent cytotoxicity (p=0.0006) and superior toxicity over photosensitizer alone (p=0.0022). METHODS Gene set enrichment analysis (GSEA) evaluated pathways during BE and EA development and quantified MUC1 gene expression. Immunohistochemistry and flow cytometry evaluated the anti-MUC1 antibody HuHMFG1 in esophageal cells of varying pathological grade. Confocal microscopy examined HuHMFG1 internalization and HuHMFG1 ADCs were created to deliver a MUC1 targeted phototoxic payload. CONCLUSIONS MUC1 is a promising target in EA. Molecular and light based targeting of MUC1 with a photosensitive ADC is effective in vitro and after development may enable treatment of locoregional tumors endoscopically.
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Affiliation(s)
- Mohammed Adil Butt
- Department for Tissue & Energy, University College London, London, UK
- Upper Gastrointestinal Service, University College London Hospitals NHS Foundation Trust, London, UK
| | - Hayley Pye
- Department for Tissue & Energy, University College London, London, UK
| | - Rehan J. Haidry
- Upper Gastrointestinal Service, University College London Hospitals NHS Foundation Trust, London, UK
| | - Dahmane Oukrif
- Department of Pathology, University College London, London, UK
| | | | - Ignazio Puccio
- Department for Tissue & Energy, University College London, London, UK
| | - Michael Gandy
- Department for Tissue & Energy, University College London, London, UK
| | - Halla W. Reinert
- Department for Tissue & Energy, University College London, London, UK
| | - Ellie Bloom
- Department for Tissue & Energy, University College London, London, UK
| | | | - Gokhan Yahioglu
- Antikor BioPharma, Stevenage Bioscience Catalyst, Hertfordshire, UK
- Department of Chemistry, Imperial College London, London, UK
| | - Mahendra P. Deonarain
- Department for Tissue & Energy, University College London, London, UK
- Antikor BioPharma, Stevenage Bioscience Catalyst, Hertfordshire, UK
- Department of Chemistry, Imperial College London, London, UK
| | - Rifat Hamoudi
- Department for Tissue & Energy, University College London, London, UK
| | | | | | - Laurence B. Lovat
- Department for Tissue & Energy, University College London, London, UK
- Upper Gastrointestinal Service, University College London Hospitals NHS Foundation Trust, London, UK
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Mansour NM, El-Serag HB, Anandasabapathy S. Barrett's esophagus: best practices for treatment and post-treatment surveillance. Ann Cardiothorac Surg 2017; 6:75-87. [PMID: 28446996 DOI: 10.21037/acs.2017.03.05] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Barrett's esophagus (BE) is a premalignant condition that increases the risk of esophageal adenocarcinoma (EAC). Significantly more common in the Western world, risk factors include increased age, male sex, white race, gastro-esophageal reflux disease (GERD), central obesity, and cigarette smoking. The rates of progression to cancer depend on the grade of Barrett's dysplasia. Screening for BE is recommended in patients with GERD and additional risk factors. Endoscopic surveillance of patients with BE likely improves overall outcomes. Advanced endoscopic imaging can help increase the efficiency of current endoscopic surveillance. Endoscopic therapy is safe and effective for the treatment of dysplastic BE and intramucosal EAC, but ongoing surveillance following treatment is necessary. This review will cover screening, surveillance, advanced imaging, chemoprevention, endoscopic treatment, and post-treatment surveillance of BE.
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Affiliation(s)
- Nabil M Mansour
- Section of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, TX, USA
| | - Hashem B El-Serag
- Section of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, TX, USA
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Mansour NM, Groth SS, Anandasabapathy S. Esophageal Adenocarcinoma: Screening, Surveillance, and Management. Annu Rev Med 2017; 68:213-227. [DOI: 10.1146/annurev-med-050715-104218] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Affiliation(s)
- Nabil M. Mansour
- Section of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, Texas 77030; ,
| | - Shawn S. Groth
- Division of Thoracic Surgery, Baylor College of Medicine, Houston, Texas 77030;
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Abstract
Incidence of oesophageal adenocarcinoma has increased exponentially in the West over the past few decades. Following detection of advanced cancers, 5-year survival rates remain bleak, making identification of early neoplasia, which has a better outcome, important. Detection of subtle oesophageal lesions during endoscopy can be challenging, and advanced imaging techniques might improve their detection. High-definition endoscopy has become a standard in most endoscopy centres, and this technology probably provides better delineation of mucosal features than standard-definition endoscopy. Various image enhancement techniques are now available with the development of new electronics and software systems. Image enhancement with chromoendoscopy using dyes has been a cost-effective option for many years, yet these techniques have been replaced in some contexts by electronic chromoendoscopy, which can be used with the press of a button. However, Lugol's chromoendoscopy remains the gold standard to identify squamous dysplasia. Identification and characterization of subtle neoplastic lesions could help to target biopsies and perform endoscopic resection for better local staging and definitive therapy. In vivo histology with techniques such as confocal endomicroscopy could make endotherapy feasible within a shorter timescale than when relying on histology on tissue samples. Once early neoplasia is identified, treatments include endoscopic resection, endoscopic submucosal dissection or various ablative techniques. Endotherapy has the advantage of being a less invasive technique than oesophagectomy, and is associated with lower mortality and morbidity. Endoscopic ablation therapies have evolved over the past few years, with radiofrequency ablation showing the best results in terms of success rates and complications in Barrett dysplasia.
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Affiliation(s)
- Jayan Mannath
- University Hospitals Coventry and Warwickshire NHS Trust, Clifford Bridge Road, Coventry, CV2 2DX, UK
| | - Krish Ragunath
- NIHR Nottingham Digestive Diseases Biomedical Research Unit, Queens Medical Centre, Nottingham University Hospitals NHS Trust, Derby Road, Nottingham, NG7 2UH, UK
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46
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Mao A. Interventional Therapy of Esophageal Cancer. Gastrointest Tumors 2016; 3:59-68. [PMID: 27904858 DOI: 10.1159/000447512] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2016] [Accepted: 06/08/2016] [Indexed: 12/15/2022] Open
Abstract
Esophageal cancer (EC) is the fourth leading cause of cancer death in China. Despite a lot of advances in diagnosis and therapy, the survival rate of patients with EC is low. There is urgent need for a variety of methods and techniques to improve the survival time and alleviate the lesions of EC. Nowadays, alternative and less invasive approaches to the treatment of ECs are being identified. Here, we review several main interventional methods at different stages of EC, including endoscopic resection, stent placement, arterial infusion, photodynamic therapy, and radiofrequency ablation. This review will focus on the indications, methods, clinical outcomes, and complications of these methods, which may help guide the way forward.
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Affiliation(s)
- Aiwu Mao
- Department of Interventional Radiology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China
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47
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Pye H, Butt MA, Reinert HW, Maruani A, Nunes JPM, Marklew JS, Qurashi M, Funnell L, May A, Stamati I, Hamoudi R, Baker JR, Smith MEB, Caddick S, Deonarain MP, Yahioglu G, Chudasama V, Lovat LB. A HER2 selective theranostic agent for surgical resection guidance and photodynamic therapy. Photochem Photobiol Sci 2016; 15:1227-1238. [PMID: 27501936 DOI: 10.1039/c6pp00139d] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
In many cancers early intervention involves surgical resection of small localised tumour masses. Inadequate resection leads to recurrence whereas overzealous treatment can lead to organ damage. This work describes production of a HER2 targeting antibody Fab fragment dual conjugated to achieve both real time near-infrared fluorescent imaging and photodynamic therapy. The use of fluorescence emission from a NIR-dye could be used to guide resection of tumour bulk, for example during endoscopic diagnosis for oesophago-gastric adenocarcinoma, this would then be followed by activation of the photodynamic therapeutic agent to destroy untreated localised areas of cancer infiltration and tumour infiltrated lymph nodes. This theranostic agent was prepared from the Fab fragment of trastuzumab initially by functional disulfide re-bridging and site-specific click reaction of a NIR-dye. This was followed by further reaction with a novel pre-activated form of the photosensitiser chlorin e6 with the exposed fragments' lysine residues. Specific binding of the theranostic agent was observed in vitro with a HER2 positive cell line and cellular near-infrared fluorescence was observed with flow cytometry. Specific photo-activity of the conjugates when exposed to laser light was observed with HER2 positive but not HER2 negative cell lines in vitro, this selectivity was not seen with the unconjugated drug. This theranostic agent demonstrates that two different photo-active functions can be coupled to the same antibody fragment with little interference to their independent activities.
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Affiliation(s)
- H Pye
- Department for Tissue & Energy, Division of Surgery & Interventional Science, University College London, Cruciform Building, Gower Street, London, WC1E 6AE, UK.
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Dolak W, Schwaighofer H, Hellmich B, Stadler B, Spaun G, Plieschnegger W, Hebenstreit A, Weber-Eibel J, Siebert F, Emmanuel K, Knoflach P, Gschwantler M, Vogel W, Trauner M, Püspök A. Photodynamic therapy with polyhematoporphyrin for malignant biliary obstruction: A nationwide retrospective study of 150 consecutive applications. United European Gastroenterol J 2016; 5:104-110. [PMID: 28405328 DOI: 10.1177/2050640616654037] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2016] [Accepted: 05/16/2016] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND Photodynamic therapy (PDT) is a palliative treatment for malignant biliary obstruction. OBJECTIVE The objective of this article is to assess the feasibility and safety of this technique. METHODS In this nationwide, retrospective study of prospectively collected clinical data, all patients treated with PDT using polyhematoporphyrin in Austria from March 2004 to May 2013 were included. Feasibility, adverse events, stent patency and mortality rates were investigated. RESULTS Eighty-eight patients (54 male, 34 female, median age 69 years) underwent 150 PDT procedures at seven Austrian referral centers for biliary endoscopy. The predominant underlying disease was Klatskin tumor (79/88). All PDT procedures were feasible without technical issues. Cholangitis was the most frequent adverse event (21/88). Stent patency was 246 days (95% CI 203-289) median and was significantly longer for metal than for plastic stents (269 vs. 62 days, p < 0.01). The median survival was 12.4 months (95% CI 9.7-14.9 m) calculated from first PDT and 15.6 months (95% CI 12.3-18.7 m) calculated from initial diagnosis. In patients suffering from biliary tract cancer, Cox regression revealed the number of PDT treatment sessions as the only independent predictor of survival at a multivariate analysis (p = 0.048). CONCLUSION PDT using polyhematoporphyrin was feasible and safe in this nationwide analysis. Survival data suggest a benefit of PDT in this unselected real-life patient population. Prospective trials comparing PDT to other palliative treatments will help to define its role in the management of malignant biliary obstruction. The study is registered at ClinicalTrials.gov number: NCT02504957.
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Affiliation(s)
- Werner Dolak
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Hubert Schwaighofer
- Department of Internal Medicine II, Medical University of Innsbruck, Innsbruck, Austria
| | - Brigitte Hellmich
- Department of Internal Medicine IV, Wilhelminenspital, Vienna, Austria
| | - Bernhard Stadler
- Department of Internal Medicine I, Klinikum Wels-Grieskirchen, Wels, Austria
| | - Georg Spaun
- Department of Surgery, Barmherzige Schwestern Linz, Linz, Austria
| | | | - Arnold Hebenstreit
- Department of Internal Medicine I, Klinikum Klagenfurt am Wörthersee, Austria
| | - Jutta Weber-Eibel
- Department of Internal Medicine I, Klinikum Klagenfurt am Wörthersee, Austria
| | - Franz Siebert
- Department of Internal Medicine, Barmherzige Brüder St. Veit an der Glan, Austria
| | - Klaus Emmanuel
- Department of Surgery, Barmherzige Schwestern Linz, Linz, Austria
| | - Peter Knoflach
- Department of Internal Medicine I, Klinikum Wels-Grieskirchen, Wels, Austria
| | | | - Wolfgang Vogel
- Department of Internal Medicine II, Medical University of Innsbruck, Innsbruck, Austria
| | - Michael Trauner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Andreas Püspök
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
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Lovat L. Another modality to treat esophageal cancer? Gastrointest Endosc 2016; 83:1140-1. [PMID: 27206582 DOI: 10.1016/j.gie.2016.02.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2016] [Accepted: 02/05/2016] [Indexed: 12/11/2022]
Affiliation(s)
- Laurence Lovat
- Division of Surgery & Interventional Science, UCL, London, United Kingdom
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50
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Macías-García F, Domínguez-Muñoz JE. Update on management of Barrett's esophagus. World J Gastrointest Pharmacol Ther 2016; 7:227-234. [PMID: 27158538 PMCID: PMC4848245 DOI: 10.4292/wjgpt.v7.i2.227] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2015] [Revised: 10/15/2015] [Accepted: 02/16/2016] [Indexed: 02/06/2023] Open
Abstract
Barrett's esophagus (BE) is a common condition that develops as a consequence of gastroesophageal reflux disease. The significance of Barrett's metaplasia is that predisposes to cancer development. This article provides a current evidence-based review for the management of BE and related early neoplasia. Controversial issues that impact the management of patients with BE, including definition, screening, clinical aspects, diagnosis, surveillance, and management of dysplasia and early cancer have been assessed.
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