AUCTORES
Globalize your Research
Research Article | DOI: https://doi.org/10.31579/2640-1045/009
*Corresponding Author: Hatem A Tawfik, Department of Endocrinology, Tunisia.
Citation: Hatem A Tawfik, Ahmad Nofal, Fatma H Ali. Meta-Analysis and Randomized Trials: Chemotherapy for Advanced Pancreatic Cancer. J. Endocrinology and Disorders. DOI:10.31579/2640-1045/009
Copyright: © 2017. Hatem A Tawfik. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Received: 25 March 2017 | Accepted: 15 June 2017 | Published: 29 June 2017
Keywords: pancreatic cancer, chemotherapy resistance, Meta-Analysis
Pancreatic cancer has an extremely poor prognosis and prolonged survival is achieved only by resection with macroscopic tumor clearance. There is a strong rationale for a neoadjuvant approach, since a relevant percentage of pancreatic cancer patients present with non-metastatic but locally advanced disease and microscopic incomplete resections are common. The objective of the present analysis was to systematically review studies concerning the effects of neoadjuvant therapy on tumor response, toxicity, resection, and survival percentages in pancreatic cancer.
No common malignancy is as rapidly and inevitably fatal as pancreatic ductal adenocarcinoma (PDA). This grim fact has driven substantial research efforts into this disease in recent decades. Unfortunately, the investment has yet to result in a meaningful increase in 5-year survival. This has prompted many pancreatic cancer researchers and advocates to redouble their efforts, but also requires one to step back and ask why the previous efforts were lacking and to consider why pancreatic cancer is so difficult to treat. The difficulties are legion. PDA is characterized by an insidious clinical syndrome, but is rarely diagnosed at a time when surgical resection is feasible. We lack markers of early detection and screening programs remain unproven even in high risk populations.
The location of the tumor in the retro peritoneum, the advanced age of patients, and the systemic effects of disease limit the options for local therapy. Chemotherapy may provide a small benefit, but most efforts to improve on the current regimens consistently and stubbornly fail in advanced clinical trials. The molecular and cellular features of ductal pancreatic tumors are aggressive and underlay multiple levels of therapeutic resistance. Non-cell-autonomous features including stromal proliferation, reduced vascular density and immune suppression also contribute to therapeutic resistance. Growing awareness of these the fundamental features of PDA has begun to guide ongoing research efforts. Clinical trials are now specifically targeting these tumor properties and actively focusing on the therapeutic implications of tumor stoma. As reviewed here, reflecting on the fundamental question of why pancreatic cancer is so difficult to treat is a necessary and informative exercise that will aid our efforts to improve patient outcomes. These efforts will lead to improvements in clinical trial design, expand our focus to include the molecular and histologic implications of novel treatment paradigms, and ultimately change the lives of our patients.
In the modern era of cancer research, pancreatic ductal adenocarcinoma (PDA) has proven to be among the most unyielding of adversaries. The oncology community has expended its entire arsenal at this disease with little effect: the 5-year survival rate has ticked up to 6% over the past 40 years, but nearly all diagnosed patients ultimately succumb to the disease. An estimated 37,390 people will die of pancreatic cancer in the US in 2012 with a similar pattern in the rest of the developed world Over 80% of them will be found to have unresectable tumors at diagnosis giving them an expected overall survival of just 6 months. There are few therapeutic options for these patients and the most efficacious are also the most burdensome. Those who do undergo surgery improve their overall survival compared with patients of a similar stage by about 10 months but must tolerate significant morbidity and face almost inevitable recurrence. Given the slow progress against this disease, one must ask the question ‘why is pancreatic cancer so hard to treat .
The particular problem of pancreatic cancer is multifactorial in its nature. The patient population in PDA is predominantly elderly and in poor overall health. There is no simple early detection method for pancreatic cancer and the earliest indications of disease are nonspecific. The tumor itself has its own peculiarities. For example, it has become apparent that PDA metastasizes microscopically early in the disease course, limiting the effectiveness of local therapies such as surgery and radiation. At the cellular level, the actual neoplastic epithelial cells at the heart of the disease harbor some of the most profoundly oncogenic alterations known to biology, and these are found at unusually high frequencies in PDA. In addition to driving growth and promoting cell survival, these alterations alter the metabolism of pancreatic cancer to one that can better support the manufacture of new cellular components. Layered on top of these high penetrance mutations is a host of rare alterations that are found in effectively unique combinations in each patient. The extent of genetic alterations in pancreatic tumors bears witness to a genomic instability phenotype that appears to play a significant role in the biology of PDA and implies an ability to rapidly develop acquired resistance to therapies that do manage to provoke an initial response. In addition to features of the tumor epithelium, PDA harbors a dense, desmoplastic stroma that can serve to limit the delivery of agents to tumors and foreshadows an incredibly complex interplay of intercellular signals that confound our ability to study the disease in vitro. Certain cell types within this stroma construct an immune-suppressed microenvironment that prevents the local immune system from clearing the tumor. Finally, PDA manifests as a syndrome, not just a mass, with systemic comorbidities that have a profoundly negative impact on quality of life.
Together, these raw observations paint a grim picture of the battle against pancreatic cancer that has at times led to a sense of nihilism. In reality, there are many signs that the research efforts of the past few decades have altered the momentum of this battle. Each of the challenges listed above has, in recent years, been the subject of intense research, leading to new ideas that are now being developed in the lab and in the clinic. For example, an understanding of the dynamics of drug delivery in PDA has led to a focus on targeted agents with desirable pharmacological properties. Another approach is to target the tumor stroma directly in order to facilitate the delivery of genotoxic agents or relieve local immune suppression. Other agents take advantage of the hypoxic microenvironment conferred by the desmoplastic stroma, or specific metabolic dependencies. Furthermore, decades of failed trials have led to improvements in clinical trial design and in the diagnostic and interventional techniques used in patients. By addressing the manifold difficulties that underpin the challenge of pancreatic cancer, a new sense of optimism is apparent. These barriers are surmountable and the nascent efforts to address them will ultimately be reflected in improved patient outcomes.
Trials were identified by searching MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials from 1966 to December 2009 as well as through reference lists of articles and proceedings of major meetings. Retrospective and prospective studies analyzing neoadjuvant radiochemotherapy, radiotherapy, or chemotherapy of pancreatic cancer patients, followed by re-staging, and surgical exploration/resection were included. Two reviewers independently extracted data and assessed study quality. Pooled relative risks and 95% confidence intervals were calculated using random-effects models. Primary outcome measures were proportions of tumor response categories and percentages of exploration and resection. A total of 111 studies (n = 4,394) including 56 phase I–II trials were analyzed. A median of 31 (interquartile range [IQR] 19–46) patients per study were included. Studies were subdivided into surveys considering initially resectable tumors (group 1) and initially non-resectable (borderline resectable/unresectable) tumors (group 2). Neoadjuvant chemotherapy was given in 96.4% of the studies with the main agents gemcitabine, 5-FU (and oral analogues), mitomycin C, and platinum compounds. Neoadjuvant radiotherapy was applied in 93.7% of the studies with doses ranging from 24 to 63 Gy. Averaged complete/partial response probabilities were 3.6% (95% CI 2%–5.5%)/30.6% (95% CI 20.7%–41.4%) and 4.8% (95% CI 3.5%–6.4%)/30.2% (95% CI 24.5%–36.3%) for groups 1 and 2, respectively; whereas progressive disease fraction was estimated to 20.9% (95% CI 16.9%–25.3%) and 20.8% (95% CI 14.5%–27.8%). In group 1, resectability was estimated to 73.6% (95% CI 65.9%–80.6%) compared to 33.2% (95% CI 25.8%–41.1%) in group 2. Higher resection-associated morbidity and mortality rates were observed in group 2 versus group 1 (26.7%, 95% CI 20.7%–33.3% versus 39.1%, 95% CI 29.5%–49.1%; and 3.9%, 95% CI 2.2%–6% versus 7.1%, 95% CI 5.1%–9.5%). Combination chemotherapies resulted in higher estimated response and resection probabilities for patients with initially non-resectable tumors (“non-resectable tumor patients”) compared to monotherapy. Estimated median survival Following resection was 23.3 (range 12–54) mo for group 1 and 20.5 (range 9–62) mo for group 2 patient
Mean scale scores in the QLQ-C30 improved more often/deteriorated less frequently in the chemotherapy group than in the best supportive care group. More patients in the chemotherapy group (36%, 17/49) had an improved or prolonged high quality of life for a minimum period of months compared to those in the best supportive care group (10%, 4/41, p <0.01). Overall survival was significantly longer in the chemotherapy group (median 6 vs. 2.5 months, p <0.01). Also, the quality-adjusted survival time was longer for patients randomized to chemotherapy (median 4 vs. 1 months, p <0.01). The effects were seen both in pancreatic cancer.
Chemotherapy
Chemotherapy was applied as neoadjuvant treatment in 107 of the 111 studies (96.4%). Different combinations of chemotherapies/agents and dosages were tested, as 56 of the studies were phase I–II trials. The main agents were gemcitabine, 5-FU (and oral analogues), mitomycin C, and platinum compounds. In the trials that used only one regimen (n = 79), 43 (54.4%) were performed using 5-FU or its oral analogues. 5-FU monotherapy was given in 14 (17.7%) of the studies. Thirty-six (45.6%) of the studies used a gemcitabine-based regimen, and of those, 18 (22.8%) studies applied gemcitabine monotherapy. 5-FU and gemcitabine combinations were used in 3 studies. Several studies compared different schemes or agents. Five studies were performed comparing gemcitabine with 5-FU or capecitabine, two studies comparing gemcitabine with cisplatin, two gemcitabine with 5-FU/cisplatin, and another three gemcitabine with 5-FU/mitomycin C. A further 16 studies included different agents and combinations (some for only few patients) Twelve trials included taxanes (docetaxel/paclitaxel) in different combinations or as monotherapy (n = 3). Five of the 107 studies included antibodies or tyrosine kinase inhibitors (bevacizumab, cetuximab, erlotinib) in the chemotherapeutic regimen. There were 44 studies using single agents (alone or in comparison) and 48 studies using combination therapies. In 15 studies both single agents and combination therapies were utilized.
Radiotherapy
In 104 of the 111 studies (93.7%) patients received neoadjuvant radiotherapy. In three studies the exact radiation dose was not given. Doses applied ranged from 24 Gy to 63 Gy .In 52 of the 104 studies that included radiotherapy the patients received doses between 45 and 50.4 Gy. In 14 studies different doses and radiation schedules were compared. Most patients received 1.8 Gy/fraction (50/104 studies), 2 Gy/fraction (15/104), or 3 Gy/fraction (10/104). In 13 studies intraoperative radiation (IORT) was applied with doses between 10 and 30 Gy. Since in most of those studies only few patients received IORT, this aspect was not further analyzed.
Tumor Response
Tumor response frequency for neoadjuvant chemo- and/or radiation therapy was evaluated in the different studies according to either radiographic or clinical response evaluation before exploration or histopathological response after resection. Six studies (5.4%) explicitly stated that the RECIST criteria were utilized. In 44 studies (39.6%) the criteria to assess tumor response were clearly stated, whereas in 61 studies (55%) criteria were either not clearly defined or not stated. For the whole study population the estimated fraction of patients with complete response was 3.9% (CI 3%–4.9%) and with partial response 29.1% (CI 24.5%–34%) Stable disease was averaged to 43.9% (CI 37.9%–50%) in all patients and tumor progression under therapy occurred by estimation in 20.8% (CI 17.3%–24.6%) of the patients.
This comprehensive review of neoadjuvant therapy in pancreatic cancer aimed to evaluate the key issues, including aspects of response and survival, and to highlight current problems and drawbacks. Neoadjuvant protocols have been analyzed with increasing frequency, as they offer a number of hypothetical advantages over adjuvant (postoperative) therapy, such as shorter therapy and higher therapy completion rates, tumor down-staging with higher (R0) resection rates, and importantly better patient selection. Thus, neoadjuvant treatment and reassessment may identify those patients (both initially resectable and non-resectable) presenting with rapid progressive or disseminated disease at restaging who therefore have a very poor prognosis and for whom surgery is unlikely to provide any benefit. On the other hand, there is the potential risk for tumor progression during neoadjuvant therapy, i.e. patients with initially resectable tumors might present with local or distant tumor progression at restaging, which might not have occurred in the setting of an initial tumor resection. In addition, neoadjuvant treatment protocols usually require histological confirmation before initiation of therapy, resulting in additional invasive diagnostic measures. Clearly, only randomized controlled trials can clarify which of the hypothetical advantages/disadvantages are real and which ones are not.
There is only one phase III randomized controlled trial being carried out comparing neoadjuvant therapy and surgery with surgery alone (NCT00335543)This multicenter trial has been recruiting patients since June 2003 and has currently enrolled less than a third of the originally planned 254 patients. Due to the exceedingly slow recruitment, the study will be terminated before reaching the target population.
In the future, phase III trials have to be carried out using already established protocols comparing neoadjuvant therapy followed by exploration and possibly resection, with immediate exploration and resection if possible (and additional standard palliative or adjuvant therapies in both arms). As our data point out, this would be especially relevant in the group of borderline resectable/unresectable tumors. As a prerequisite for such trials, standard definitions of resectability and objective computed tomography criteria should be applied.
The present analysis provides the most comprehensive review regarding neoadjuvant therapies in resectable and non-resectable pancreatic cancers to date—thus, the best actual available evidence for response rates, treatment toxicities, resection rates, morbidity and mortality, and survival estimates. The most important findings are that in the group of resectable tumor patients, resection and survival rates after neoadjuvant therapy are similar to the ones observed in primarily resected tumor that are treated by adjuvant therapy. Thus, in this group of patients, the current data do not point to an obvious advantage of neoadjuvant therapy. In contrast, in patients initially staged locally advanced/unresectable, approximately one third of the patients can be resected following neoadjuvant therapy with comparable survival rates as patients who were staged as resectable before treatment. Due to the heterogeneity of applied protocols, data regarding the optimal chemotherapeutic and radiotherapeutic regimen cannot be extrapolated; however, the data suggest that combination chemotherapies result in higher response rates, which is reflected by higher resection rates at least in the group of initially non-resectable tumor patients. Future trials have first to clearly establish the role of neoadjuvant therapy specifically in locally advanced/unresectable tumors and subsequently to define optimal treatment protocols. In addition, common definitions for resectability/non-resectability as well as for response evaluation should be applied. As of now, the available data strongly suggest that patients with locally advanced/unresectable tumors should be included in neoadjuvant protocols and subsequently be re-evaluated for resection, which is possible in a relevant number of patients.
Clearly Auctoresonline and particularly Psychology and Mental Health Care Journal is dedicated to improving health care services for individuals and populations. The editorial boards' ability to efficiently recognize and share the global importance of health literacy with a variety of stakeholders. Auctoresonline publishing platform can be used to facilitate of optimal client-based services and should be added to health care professionals' repertoire of evidence-based health care resources.
Journal of Clinical Cardiology and Cardiovascular Intervention The submission and review process was adequate. However I think that the publication total value should have been enlightened in early fases. Thank you for all.
Journal of Women Health Care and Issues By the present mail, I want to say thank to you and tour colleagues for facilitating my published article. Specially thank you for the peer review process, support from the editorial office. I appreciate positively the quality of your journal.
Journal of Clinical Research and Reports I would be very delighted to submit my testimonial regarding the reviewer board and the editorial office. The reviewer board were accurate and helpful regarding any modifications for my manuscript. And the editorial office were very helpful and supportive in contacting and monitoring with any update and offering help. It was my pleasure to contribute with your promising Journal and I am looking forward for more collaboration.
We would like to thank the Journal of Thoracic Disease and Cardiothoracic Surgery because of the services they provided us for our articles. The peer-review process was done in a very excellent time manner, and the opinions of the reviewers helped us to improve our manuscript further. The editorial office had an outstanding correspondence with us and guided us in many ways. During a hard time of the pandemic that is affecting every one of us tremendously, the editorial office helped us make everything easier for publishing scientific work. Hope for a more scientific relationship with your Journal.
The peer-review process which consisted high quality queries on the paper. I did answer six reviewers’ questions and comments before the paper was accepted. The support from the editorial office is excellent.
Journal of Neuroscience and Neurological Surgery. I had the experience of publishing a research article recently. The whole process was simple from submission to publication. The reviewers made specific and valuable recommendations and corrections that improved the quality of my publication. I strongly recommend this Journal.
Dr. Katarzyna Byczkowska My testimonial covering: "The peer review process is quick and effective. The support from the editorial office is very professional and friendly. Quality of the Clinical Cardiology and Cardiovascular Interventions is scientific and publishes ground-breaking research on cardiology that is useful for other professionals in the field.
Thank you most sincerely, with regard to the support you have given in relation to the reviewing process and the processing of my article entitled "Large Cell Neuroendocrine Carcinoma of The Prostate Gland: A Review and Update" for publication in your esteemed Journal, Journal of Cancer Research and Cellular Therapeutics". The editorial team has been very supportive.
Testimony of Journal of Clinical Otorhinolaryngology: work with your Reviews has been a educational and constructive experience. The editorial office were very helpful and supportive. It was a pleasure to contribute to your Journal.
Dr. Bernard Terkimbi Utoo, I am happy to publish my scientific work in Journal of Women Health Care and Issues (JWHCI). The manuscript submission was seamless and peer review process was top notch. I was amazed that 4 reviewers worked on the manuscript which made it a highly technical, standard and excellent quality paper. I appreciate the format and consideration for the APC as well as the speed of publication. It is my pleasure to continue with this scientific relationship with the esteem JWHCI.
This is an acknowledgment for peer reviewers, editorial board of Journal of Clinical Research and Reports. They show a lot of consideration for us as publishers for our research article “Evaluation of the different factors associated with side effects of COVID-19 vaccination on medical students, Mutah university, Al-Karak, Jordan”, in a very professional and easy way. This journal is one of outstanding medical journal.
Dear Hao Jiang, to Journal of Nutrition and Food Processing We greatly appreciate the efficient, professional and rapid processing of our paper by your team. If there is anything else we should do, please do not hesitate to let us know. On behalf of my co-authors, we would like to express our great appreciation to editor and reviewers.
As an author who has recently published in the journal "Brain and Neurological Disorders". I am delighted to provide a testimonial on the peer review process, editorial office support, and the overall quality of the journal. The peer review process at Brain and Neurological Disorders is rigorous and meticulous, ensuring that only high-quality, evidence-based research is published. The reviewers are experts in their fields, and their comments and suggestions were constructive and helped improve the quality of my manuscript. The review process was timely and efficient, with clear communication from the editorial office at each stage. The support from the editorial office was exceptional throughout the entire process. The editorial staff was responsive, professional, and always willing to help. They provided valuable guidance on formatting, structure, and ethical considerations, making the submission process seamless. Moreover, they kept me informed about the status of my manuscript and provided timely updates, which made the process less stressful. The journal Brain and Neurological Disorders is of the highest quality, with a strong focus on publishing cutting-edge research in the field of neurology. The articles published in this journal are well-researched, rigorously peer-reviewed, and written by experts in the field. The journal maintains high standards, ensuring that readers are provided with the most up-to-date and reliable information on brain and neurological disorders. In conclusion, I had a wonderful experience publishing in Brain and Neurological Disorders. The peer review process was thorough, the editorial office provided exceptional support, and the journal's quality is second to none. I would highly recommend this journal to any researcher working in the field of neurology and brain disorders.
Dear Agrippa Hilda, Journal of Neuroscience and Neurological Surgery, Editorial Coordinator, I trust this message finds you well. I want to extend my appreciation for considering my article for publication in your esteemed journal. I am pleased to provide a testimonial regarding the peer review process and the support received from your editorial office. The peer review process for my paper was carried out in a highly professional and thorough manner. The feedback and comments provided by the authors were constructive and very useful in improving the quality of the manuscript. This rigorous assessment process undoubtedly contributes to the high standards maintained by your journal.
International Journal of Clinical Case Reports and Reviews. I strongly recommend to consider submitting your work to this high-quality journal. The support and availability of the Editorial staff is outstanding and the review process was both efficient and rigorous.
Thank you very much for publishing my Research Article titled “Comparing Treatment Outcome Of Allergic Rhinitis Patients After Using Fluticasone Nasal Spray And Nasal Douching" in the Journal of Clinical Otorhinolaryngology. As Medical Professionals we are immensely benefited from study of various informative Articles and Papers published in this high quality Journal. I look forward to enriching my knowledge by regular study of the Journal and contribute my future work in the field of ENT through the Journal for use by the medical fraternity. The support from the Editorial office was excellent and very prompt. I also welcome the comments received from the readers of my Research Article.
Dear Erica Kelsey, Editorial Coordinator of Cancer Research and Cellular Therapeutics Our team is very satisfied with the processing of our paper by your journal. That was fast, efficient, rigorous, but without unnecessary complications. We appreciated the very short time between the submission of the paper and its publication on line on your site.
I am very glad to say that the peer review process is very successful and fast and support from the Editorial Office. Therefore, I would like to continue our scientific relationship for a long time. And I especially thank you for your kindly attention towards my article. Have a good day!
"We recently published an article entitled “Influence of beta-Cyclodextrins upon the Degradation of Carbofuran Derivatives under Alkaline Conditions" in the Journal of “Pesticides and Biofertilizers” to show that the cyclodextrins protect the carbamates increasing their half-life time in the presence of basic conditions This will be very helpful to understand carbofuran behaviour in the analytical, agro-environmental and food areas. We greatly appreciated the interaction with the editor and the editorial team; we were particularly well accompanied during the course of the revision process, since all various steps towards publication were short and without delay".
I would like to express my gratitude towards you process of article review and submission. I found this to be very fair and expedient. Your follow up has been excellent. I have many publications in national and international journal and your process has been one of the best so far. Keep up the great work.
We are grateful for this opportunity to provide a glowing recommendation to the Journal of Psychiatry and Psychotherapy. We found that the editorial team were very supportive, helpful, kept us abreast of timelines and over all very professional in nature. The peer review process was rigorous, efficient and constructive that really enhanced our article submission. The experience with this journal remains one of our best ever and we look forward to providing future submissions in the near future.
I am very pleased to serve as EBM of the journal, I hope many years of my experience in stem cells can help the journal from one way or another. As we know, stem cells hold great potential for regenerative medicine, which are mostly used to promote the repair response of diseased, dysfunctional or injured tissue using stem cells or their derivatives. I think Stem Cell Research and Therapeutics International is a great platform to publish and share the understanding towards the biology and translational or clinical application of stem cells.
I would like to give my testimony in the support I have got by the peer review process and to support the editorial office where they were of asset to support young author like me to be encouraged to publish their work in your respected journal and globalize and share knowledge across the globe. I really give my great gratitude to your journal and the peer review including the editorial office.
I am delighted to publish our manuscript entitled "A Perspective on Cocaine Induced Stroke - Its Mechanisms and Management" in the Journal of Neuroscience and Neurological Surgery. The peer review process, support from the editorial office, and quality of the journal are excellent. The manuscripts published are of high quality and of excellent scientific value. I recommend this journal very much to colleagues.
Dr.Tania Muñoz, My experience as researcher and author of a review article in The Journal Clinical Cardiology and Interventions has been very enriching and stimulating. The editorial team is excellent, performs its work with absolute responsibility and delivery. They are proactive, dynamic and receptive to all proposals. Supporting at all times the vast universe of authors who choose them as an option for publication. The team of review specialists, members of the editorial board, are brilliant professionals, with remarkable performance in medical research and scientific methodology. Together they form a frontline team that consolidates the JCCI as a magnificent option for the publication and review of high-level medical articles and broad collective interest. I am honored to be able to share my review article and open to receive all your comments.
“The peer review process of JPMHC is quick and effective. Authors are benefited by good and professional reviewers with huge experience in the field of psychology and mental health. The support from the editorial office is very professional. People to contact to are friendly and happy to help and assist any query authors might have. Quality of the Journal is scientific and publishes ground-breaking research on mental health that is useful for other professionals in the field”.
Dear editorial department: On behalf of our team, I hereby certify the reliability and superiority of the International Journal of Clinical Case Reports and Reviews in the peer review process, editorial support, and journal quality. Firstly, the peer review process of the International Journal of Clinical Case Reports and Reviews is rigorous, fair, transparent, fast, and of high quality. The editorial department invites experts from relevant fields as anonymous reviewers to review all submitted manuscripts. These experts have rich academic backgrounds and experience, and can accurately evaluate the academic quality, originality, and suitability of manuscripts. The editorial department is committed to ensuring the rigor of the peer review process, while also making every effort to ensure a fast review cycle to meet the needs of authors and the academic community. Secondly, the editorial team of the International Journal of Clinical Case Reports and Reviews is composed of a group of senior scholars and professionals with rich experience and professional knowledge in related fields. The editorial department is committed to assisting authors in improving their manuscripts, ensuring their academic accuracy, clarity, and completeness. Editors actively collaborate with authors, providing useful suggestions and feedback to promote the improvement and development of the manuscript. We believe that the support of the editorial department is one of the key factors in ensuring the quality of the journal. Finally, the International Journal of Clinical Case Reports and Reviews is renowned for its high- quality articles and strict academic standards. The editorial department is committed to publishing innovative and academically valuable research results to promote the development and progress of related fields. The International Journal of Clinical Case Reports and Reviews is reasonably priced and ensures excellent service and quality ratio, allowing authors to obtain high-level academic publishing opportunities in an affordable manner. I hereby solemnly declare that the International Journal of Clinical Case Reports and Reviews has a high level of credibility and superiority in terms of peer review process, editorial support, reasonable fees, and journal quality. Sincerely, Rui Tao.
