AUCTORES
Globalize your Research
Case Report | DOI: https://doi.org/10.31579/2640-1053/099
1 Dept of Surgical Oncology, Currae Cancer & Multispeciality Hospital, Mumbai, India
2 Dept of Surgical Oncolog, Terna Superspeciality Hospital, Nerul, New Mumbai, India
3 Dept of Ophthalmology, Conwest & Jain Superspeciality Eye Hospital, Mumbai, India
*Corresponding Author: Sachin S Kadam, Dept of Surgical Oncology, Currae Cancer & Multispecialty Hospital, Mumbai, India.
Citation: Sachin S Kadam, S Phadke, T Kadam. (2021) Karapandzic Flap for Functional & Cosmetic Reconstruction of Lower Lip Cancer with Review of Literature. Cancer Research and Cellular Therapeutics. 5(5); Doi: 10.31579/2640-1053/099
Copyright: © 2021 Sachin S Kadam, 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: 13 September 2021 | Accepted: 27 September 2021 | Published: 08 October 2021
Keywords: lip cancer; karapandzic flap; cosmesis; reconstructive surgery; squamous cell carcinoma
The incidence and prevalence of lip and oral cavity cancer has increased over the last decade, worldwide and in India. It ranks at 1st position in males in india, all ages, in 2020. Lips are essential organ of the body which carries dynamic role in facial expression, speech, sensuality, deglutition. Resection of central, large, lower lip cancer creates a more than 2/3rd large defect. Covering of this defect with maintenance of oral competency is a difficult task for a treating surgeon. Number of techniques are described for covering of large lower lip defects. Out of these techniques, karapandzic flap is a successful, accepted, simple, easy to learn reconstructive procedure with good cosmetic results. It is a modification of Gillie’s fan flap and it involves unilateral or bilateral full-thickness circumoral advancement-rotation flaps. The feature which distinguishes it from other techniques is preservation of neuro-vascular integrity, symmetry and oral competency. We are reporting a case of an elderly gentleman with large, central, lower lip cancer who underwent oncological resection with reconstruction by karapandzic flap technique.
Human lips are considered as the dynamic organ of the body as they are responsible for multiple functions like facial expression, articulation of speech, deglutition, and containment of salivary secretions. Lips are responsible for one’s quality of life, self-esteem and facial appeal [1]. Squamous cell carcinoma of lip is considered as most common and aggressive malignancy. In 95% of cases lower lips are involved compared to only 5 % involvement of upper lip [2] .Worldwide , number of new cases in 2020 , both sexes , all ages and number of death in 2020, both sexes, all ages were 3,77,713 and 1,77,757 respectively [3]. In India, lip and oral cavity cancer ranks at 1st position in males, all ages with incidence 16.2 % and 13.5% incidence in both sexes, all ages in 2020 [4]. Depending on the extent and depth of the tumor, the resection procedure works and depending on the defect of the lower lip, the reconstruction procedure will be planned. Full thickness loss of more than ½ to 1/3rd of lower lip poses a challenge to the treating surgeon as it’s a difficult task to cover the defect with maintenance of commissure competence, cosmesis, symmetry and preservation of sensation.
Number of techniques are described and available for reconstruction of lower lip. Karapandzic flap is a technique for reconstruction of full thikness, large, centrally located defects of the lower lip and, to a lesser extent, the upper lip [5]. The technique involves unilateral or bilateral full-thickness circumoral advancement-rotation flaps [6]. The outstanding feature of this flap reconstruction technique is preservation of the neural and vascular structures which helps in maintaining oral competency and sensory function. We are reporting a case of an elderly gentleman with large, central, lower lip cancer who underwent oncological resection with reconstruction by karapandzic flap.
A 51 year old gentleman with no co-morbidity with Eastern Cooperative Oncology Group Performance Status 1 (ECOG –PS 1) presented to our clinic with ulero-proliferative lesion over the lower lip for the last 4 months. He had an addiction of tobacco chewing and he used to consume it, 8-9 times per day for the last 30 years. Family history, past history, medical history and surgical history were not relevant. On clinical examination, an ulcero-proliferative growth of size 3x3cm was present over the lower lip at central region located at 2cm left from right commissure and 1.5cm right from left commissure [ Fig 2 ] . No other positive findings were noted in the oral cavity. Bilateral submandibular lymph nodes were palpable. He underwent CECT (Contrast Enhanced Computed Tomography) of oral cavity, neck and chest which was already advised by primary general practitioner. CECT was also suggestive of same findings with absent disease in the chest [Fig. 1]. We did wedge biopsy from the lesion which was indicative of squamous cell carcinoma. Case was discussed in our institutional multidisciplinary tumor board and plan of upfront surgery was decided for him. As per board decision, we had planned surgery after getting fitness from physician and anesthesist. He underwent surgery with wide local excision of the lower lip lesion with bilateral selective neck dissection (Level I to IV) with reconstruction by karapandzic flap.
After excision of the lesion [Fig. 3, 4], bilateral nasolabial folds are mobilised maintaining neurovascular structures. These mobilised full thickness circumoral advancement flaps are rotated and a new lower lip was reconstructed [Fig. 5, 6]. Every care was taken to maintain the oral competency [Fig. 7]. Patient was started on oral feeding from postoperative day two. Postoperative course was uneventful and he was discharged on 5th postoperative day. Final histopathology report was indicative of moderately differentiated squamous cell carcinoma with tumor size 3 x 2.5 x 1.5 cm and all margins were free from tumor except inner mucosal margin which was 0.3cm away from the tumor ( close margin ) with no lymph node metastasis ( 0/47 lymph nodes ) . AJCC 8th edition staging was p T2 pN0 pM0. Case was re-discussed in our board meeting for adjuvant treatment planning. Patient had been advised adjuvant radiation in view of close inner mucosal margin. However, patient didn’t turn up for radiation. Hence, he had been advised close follow up as per our institutional follow up protocol. His swallowing function, speech was unaffected with no microstomia and no functional impairment. After completion of follow up period of one year post treatment [Fig. 8], he is still disease free.
Lips are considered as an organ of expression, feeling and sensuality. Facial cosmesis will be affected if lips lost their functional integrity. Hence, it is very important for the reconstructive surgeon to maintain its normal form and shape. In 1768, Louis is the first person who described the method of v-shaped excision of the lesion followed by primary closure [7]. Large size, full thickness defects of the lower lip requires a larger amount of tissue to cover up the defect which can provide desired functional outcome. Fujimori [8] and Nakajima et al [9] recommended some of the basic measures before selecting a reconstructive procedure -
Local flaps should be preferred with innervated muscle.
There should not be any microstomia in a newly reconstructed lip
All suture lines should be in natural facial creases.
The flaps should be large enough to contain whole elements of lip tissue.
The available techniques described for reconstruction of the lower lip with primary closure are ‘‘Y’’, ‘‘W’’, ‘‘M’’, or Z plasties for defects affecting less than one-third of the lip. For more extensive defects, the techniques available are the Abbe, Estlander, Gillies, Bernard-Burow flaps or combinations of these [10, 11]. Webster-Bernard technique gives good results which creates new lower lip with medial advancement of the cheek tissue, however, significant scarring will be there in postoperative period [12].
Bakamjian [13] described the use of the tongue flap as a source of tissue in major lip reconstructions.
Mchug described reconstruction of large lip defects including the whole of the lower lip by using neurovascular island flap. The sensory function, muscular function and sphincter functions are maintained in this technique [14]. Rayner [15] described the technique of musculo-mucosal flaps from the cheeks. Johanson et al. [16] described the step ladder technique for lower lip reconstruction by mobilising lip tissue opposite to site of defect. Abbe or Estlander cross-lip transposition flaps are described for the reconstruction of defects of the lateral parts of the lower lip, however, their extent is limited to upper lip only [17].
Gillies and Millard [18] described a fan flap for reconstruction of the lower lip which is based on upper labial artery and it involves rotation of the naso-labial folds with advancement toward midline .However, this flap did not work in preserving neuro-vascular structures and it may result in formation of microstomia. Karapandzic [19] described a technique which is a modification of the Gillies fan flap and it was named as karapandzic flap. The main arterial supply of karapandzic flap is from the inferior labial artery, which is a branch of the facial artery. It provides numerous perforators through the orbicularis oris muscle to the overlying skin. Sensory nerve supply to the lower lip is from the mental nerve which is a terminal branch of inferior alveolar nerve which is in turn a branch of mandibular division of the trigeminal nerve. The principle feature of this flap is preservation of neuro-vascular structures, thus the competency of oral commissure and sensory and motor innervation are preserved with avoidance of additional transaction of orbicularis oris muscle [19]. Though the flap maintains the competency of oral commissure, in case of large lower lip defects, microstomia is unavoidable. However, it can be corrected with commissuroplasty [20]. In the index case, all dissection was carried out carefully with preserving neuro-vascular bundle and avoiding injury to orbicularis oris muscle with roation-advancement of naso-labial folds. Oral competency was maintained with maintenance of sensory and motor functions.
Karapandzic flap is a successful, simple, easy to learn technique for the reconstruction of central 2/3rd of the lower lip with preservation of motor and sensory supply with maintaining oral competency and produces good cosmetic results.
Human subject: Informed consent was obtained from the patient for being included in the study.
The authors declare that they have no conflict of interests.
All authors have declared that no financial support was received from any organization for the submitted work.
All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work.
All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.
Not applicable.
An informed consent to publish this case was obtained from the patient.
Not applicable.
Not applicable
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.
Clinical Cardiology and Cardiovascular Interventions I testity the covering of the peer review process, support from the editorial office, and quality of the journal.
Clinical Cardiology and Cardiovascular Interventions, we deeply appreciate the interest shown in our work and its publication. It has been a true pleasure to collaborate with you. The peer review process, as well as the support provided by the editorial office, have been exceptional, and the quality of the journal is very high, which was a determining factor in our decision to publish with you.
The peer reviewers process is quick and effective, the supports from editorial office is excellent, the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews journal clinically in the future time.
Clinical Cardiology and Cardiovascular Interventions, I would like to express my sincerest gratitude for the trust placed in our team for the publication in your journal. It has been a true pleasure to collaborate with you on this project. I am pleased to inform you that both the peer review process and the attention from the editorial coordination have been excellent. Your team has worked with dedication and professionalism to ensure that your publication meets the highest standards of quality. We are confident that this collaboration will result in mutual success, and we are eager to see the fruits of this shared effort.
Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, I hope this message finds you well. I want to express my utmost gratitude for your excellent work and for the dedication and speed in the publication process of my article titled "Navigating Innovation: Qualitative Insights on Using Technology for Health Education in Acute Coronary Syndrome Patients." I am very satisfied with the peer review process, the support from the editorial office, and the quality of the journal. I hope we can maintain our scientific relationship in the long term.
Dear Monica Gissare, - Editorial Coordinator of Nutrition and Food Processing. ¨My testimony with you is truly professional, with a positive response regarding the follow-up of the article and its review, you took into account my qualities and the importance of the topic¨.
Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, The review process for the article “The Handling of Anti-aggregants and Anticoagulants in the Oncologic Heart Patient Submitted to Surgery” was extremely rigorous and detailed. From the initial submission to the final acceptance, the editorial team at the “Journal of Clinical Cardiology and Cardiovascular Interventions” demonstrated a high level of professionalism and dedication. The reviewers provided constructive and detailed feedback, which was essential for improving the quality of our work. Communication was always clear and efficient, ensuring that all our questions were promptly addressed. The quality of the “Journal of Clinical Cardiology and Cardiovascular Interventions” is undeniable. It is a peer-reviewed, open-access publication dedicated exclusively to disseminating high-quality research in the field of clinical cardiology and cardiovascular interventions. The journal's impact factor is currently under evaluation, and it is indexed in reputable databases, which further reinforces its credibility and relevance in the scientific field. I highly recommend this journal to researchers looking for a reputable platform to publish their studies.
Dear Editorial Coordinator of the Journal of Nutrition and Food Processing! "I would like to thank the Journal of Nutrition and Food Processing for including and publishing my article. The peer review process was very quick, movement and precise. The Editorial Board has done an extremely conscientious job with much help, valuable comments and advices. I find the journal very valuable from a professional point of view, thank you very much for allowing me to be part of it and I would like to participate in the future!”
Dealing with The Journal of Neurology and Neurological Surgery was very smooth and comprehensive. The office staff took time to address my needs and the response from editors and the office was prompt and fair. I certainly hope to publish with this journal again.Their professionalism is apparent and more than satisfactory. Susan Weiner
My Testimonial Covering as fellowing: Lin-Show Chin. The peer reviewers process is quick and effective, the supports from editorial office is excellent, the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews.
My experience publishing in Psychology and Mental Health Care was exceptional. The peer review process was rigorous and constructive, with reviewers providing valuable insights that helped enhance the quality of our work. The editorial team was highly supportive and responsive, making the submission process smooth and efficient. The journal's commitment to high standards and academic rigor makes it a respected platform for quality research. I am grateful for the opportunity to publish in such a reputable journal.
My experience publishing in International Journal of Clinical Case Reports and Reviews was exceptional. I Come forth to Provide a Testimonial Covering the Peer Review Process and the editorial office for the Professional and Impartial Evaluation of the Manuscript.
