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Siberian journal of oncology

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Vol 21, No 2 (2022)
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https://doi.org/10.21294/1814-4861-2022-21-2

EPIDEMIOGICAL STUDIES

5-11 455
Abstract

According to the who data, lung cancer (lc) is the most common cancer (nearly 13,0 %) and prostate cancer (pc) is the second most common cancer (11,0 %) in men worldwide. In the chelyabinsk region, pc has been the most common cancer since 2019, accounting for 18,3 % of all cancer cases in males, and lc has become the second most common cancer, accounting for 6,8 %.

The purpose of the study was to evaluate the epidemiological situation in terms of the most common cancers (lc and pc) in a male population of rural municipal areas in the constituent entity of the Russian Federation.

Material and methods. The incidence and mortality of lung and prostate cancers were analyzed in 1020 males from five rural municipal districts of the chelyabinsk Region, territorially included in the magnitogorsk oncological cluster. Data were obtained from the population cancer Registry of the chelyabinsk Region for 2010–2019.

Results. Over a ten-year period, the average detection rates for lc and pc were 103.59 ± 3.28 and 50.75 ± 4.86, respectively per 100,000 men in rural municipal areas. The average 1-year mortality rates from lc and pc were 59.33 ± 2.14 % and 21.11 ± 2.89 %, respectively. The average overall lc mortality was 85.44 ± 5.1 deaths per 100,000 men and the average overall pc mortality was 23.04 ± 1.26 deaths per 100,000.

Discussion. The rates of the 1-year mortality from lc and pc, as well as the rates of the overall mortality from lc in men of rural municipal areas were higher than those in urban areas, demonstrating the tendency to increase.

Conclusion. To ensure access to oncology medicine for patients in rural areas, private medical oncology clinics are involved on the basis of public-private partnership.

CLINICAL STUDIES

12-23 711
Abstract

Purpose of the study. To determine and compare the diagnostic efficacy of planar scintigraphy, SPECT (including SPECT/CT) and intraoperative gamma probe radiometry in the detection of sentinel lymph nodes (SLN) in patients with breast cancer.

Material and methods. The study included 200 patients with diagnosed breast cancer who underwent SLN biopsy in the period 2020–2021. To identify SLN s, all patients underwent lymphoscintigraphy with a 99mtc-labeled colloidal radiopharmaceutical one day before surgery. Planar lymphoscintigraphy was performed on 200 patients included into the study, 181 underwent examination in the volume of SPECT or SPECT/CT (147 and 34 studies, respectively). The SLN was detected intraoperatively using a portable gamma probe (n=200). Subsequent histological examination determined the presence of lymphoid tissue and the status of the removed SLN.

Results. SLN were detected in a comprehensive study (planar and tomographic studies) in all 200 patients studied (100 %), while planar scintigraphy did not visualize any SLN in 6 (3 %) cases, but they were determined during examination in tomographic mode. Also, in some cases, additional SLN were determined during tomography, which were not considered in the planar study. In 95 % of cases, SLN were localized in the axillary region. All non-axillary slns were identified on tomograms. The sensitivity of SPECT for SLN detection was 100 % (ci 98.0–100 %), which was higher than the sensitivity of planar scintigraphy and gamma probe (97.0 %, ci 96.5–97.4 % and 97.0 %, ci 96.1–97.4 %, respectively). The PPV values were also high (99.5 %, ci 99.0–100 % for planar scintigraphy, 99.5 %, ci 98.6–100 % for gamma probe and 98.3 %, ci 95.2–99.7 % for SPECT.

Conclusion. Nuclear medicine imaging of sln with lymphotropic radiopharmaceuticals in patients with breast cancer is an effective and reliable method of navigation during surgery to perform a biopsy. SPECT and SPECT/CT can identify more lymph nodes than planar scintigraphy, improving their anatomical localization, and reducing the false negative rate. The diagnostic performance of SPECT/CT and SPECT is believed to be superior to that of planar lymphoscintigraphy and intraoperative navigation in detecting SLN.

24-37 632
Abstract

Objective. To study clinical and pathological characteristics of gastric cancer in patients aged younger and older than 50 years, who received anticancer treatment including surgery, as well as to identify prognostic factors for overall survival of these patients.

Material and methods. A retrospective study of surgical treatment outcomes was conducted in 350 gastric cancer patients, who were divided into 2 groups. The study group included 34 (9.71 %) patients aged 50 years and younger and the control group consisted of 316 (90.29 %) patients aged 51 years and older.

Results. The analysis of treatment outcomes and survival rates was carried out. The diffuse-type gastric cancer was more frequently diagnosed in younger than in older patients (p<0.001), and asymptomatic disease often present in younger patients (p<0.001). There were no differences in the extent of surgery between the groups (p=0.613). The overall survival rate was lower in the control group than in the study group (p=0.002). The multivariate analysis revealed that a worse prognosis was observed in patients of the control group (hr=12.71), with regional lymph node metastases (hr=2.64), distant metastases (hr=1.83), iii/iv stage of the disease (hr=2.01), lymphovascular (hr=3.15) and perineural invasion (hr=2.46), as well as with postoperative complications (hr=2.12). Adjuvant chemotherapy improved the disease prognosis (hr=0.35).

Conclusion. Specific clinical and pathological features predicted survival of gastric cancer patients aged younger and older 50 years.

38-44 499
Abstract

The purpose of the study was to identify risk factors for the development of early postoperative complications after cryoablation of localized kidney cancer.

Material and methods. The study included 56 patients with kidney cancer who underwent cryoablation as a treatment option. Cryoablation for localized kidney cancer was performed using the liquid nitrogen-based cryogenic device. Early postoperative complications during the 30-day follow-up period were classified according to the clavien-dindo system.

Results. The univariate analysis included 9 predictor factors that affected the risk of developing complications after kidney cancer cryoablation. However, only 2 factors were associated with an increased risk of postoperative complications: tumor localization in the right kidney (odds ratio – 0.2619, 95 % confidence interval – 0.08553–0.8020; p=0.019) and localization in the upper kidney pole (odds ratio 0.09955, 95 % confidence interval – 0.01872–0.5292; p=0.0068).

Conclusion. Liquid nitrogen-based cryoablation therapy for localized kidney cancer was shown to be an effective and safe treatment option with a low incidence of postoperative complications.

LABORATORY AND EXPERIMENTAL STUDIES

45-54 1768
Abstract

Introduction. Ovarian cancer (OC) is the third most common gynecological cancer with the worst prognosis and highest mortality rate. The progression of OC can be accompanied by the detrimental functions of the components of the tumor microenvironment, including tumor-associated macrophages (TAMs).

The purpose of the study to analyze distribution and morphological phenotype of TAMs in tumor tissue of patients with high-grade serous ovarian cancer (HGSOC).

Material and methods. Formalin fixed paraffin embedded tissue sections were obtained from ovarian cancer patients after tumor resection. The protein expression of general macrophage marker CD68 and M2-like markers CD206, CD163 and stabilin-1, belonging to scavenger receptors, was analysed by immunohistochemical staining in tumor tissue. Histological assessment of TAM distribution was performed by pathologist. Immunofluorescent analysis/confocal microscopy was applied to establish the co-expression of CD68 with the main macrophage scavenger receptors.

Results. We were able to find giant CD 68-positive macrophages with foamy cytoplasm in ovarian tumor tissue. The accumulation of these tams was specific only for patients with advanced stage (IIIC and IV stages). The presence of foamlike tams had a statistical tendency to be associated with ovarian cancer progression, including metastasis and recurrence. The distribution of stabilin-1-positive macrophages was matched to CD68 expression in almost all cases, as was shown by IHC. Confocal microscopy confirmed that stabilin-1 was expressed in at least 50 % of giant tams. If analysis of tumor samples also demonstrated co-expression of other scavenger receptors, CD163 and CD36, in foam-like cells. Similar to IHC, in most samples the expression of CD206 in tams of foam-like morphology was limited.

Conclusion. For the first time we demonstrated the accumulation of giant macrophages with fluffy foam cytoplasm in the tumor tissue of treated patients with advanced ovarian cancer. Such macrophages express diverse scavenger receptors (stabilin-1, CD163, CD 36), thus indicating a high clearance activity of giant TAMs.

55-64 608
Abstract

Background. Various tumor control genes and microRNAs (miRNa) play an important role in the development and progression of colorectal cancer (CRC). the expression of these genes can differ significantly in tumor and adjacent healthy tissues. there is no exact data at what distance from the tumor the adjacent healthy tissue is located in terms of gene expression.

The aim of the investigation was to study the tumor control genes (E2F3, TGFB, NFKB, KLF-12, EGFR and MMP9), as well as the microRNA genes (microRNA-15, -16, -21 and -210) expression profiles in tumor and adjacent healthy tissues.

Material and methods. the study included 19 patients diagnosed with colorectal cancer. the tumor control genes (E2F3, TGFB, NFKB, KLF-12, EGFR and MMP9), as well as the miRNA genes (miRNA-15, -16, -21 and -210) expression levels were investigated in tumor and adjacent normal tissue samples taken during colonoscopy.

Results. a decrease in the level of expression of E2F3 (median 3,73, Q1-Q3 2,64 Reu vs. median 6.5, Q1-Q3 6,39 REU, p=0,01) and miRNA-16 (median 2,83, Q1-Q3 4,74 REU vs. median 4,29, Q1-Q3 3,73 REU, p=0,027) and an increase in the expression level of miRNA-21 (median 2,64, Q1-Q3 1,38 REU vs. median 1,41, Q1-Q3 1,21 REU, p<0,001) were found in tumor tissue compared to normal tissue of patients with CRC.

Conclusion. significant differences in the E2F3, miRNA-16 and miRNA-21 gene expressions were revealed. an increased level of E2F3 and miRNA-16 expressions at a distance of 1–2 cm from the tumor may be a predictor of tumor recurrence and progression, and an increased miRNA-21 expression in tumor tissue as compared to adjacent tissue may be a negative prognostic factor. this information can be used in further clinical research.

65-80 775
Abstract

The aim of the study was to identify fatty acids (FA) of erythrocyte membranes and blood serum, which can serve as potential biomarkers for early detection of colorectal cancer.

Material and methods. the study involved 65 patients with stage I-II CRC (mean age 63,3 ± 9,6 years (30 men, 35 women) and 35 people in the comparison group, matched by age and sex. the composition of fatty acids of erythrocyte membranes and blood serum was studied using a gc/ms system based on three agilent 7000B quadrupoles (USA). methods of the MATLAB software (R2019a, MathWorks) and the R programming language were used for statistical processing: t-test, unsupervised principal component analysis (PCA), Fold change, Volcano plot, machine learning method (Random Forest), Roc analysis, Heatmaps.

Results. patients with stage I-II CRC showed a decrease in the level of saturated, individual monounsaturated fatty acids and a highly significant increase in the most of the polyunsaturated fatty acids with a predominance of omega-3. For most of the fatty acid levels, significant differences in erythrocyte membranes and serum between the groups were found. the levels of erythrocyte myristic, pentadecanoic, 7-palmitoleic, saturated/polyunsaturated Fa ratios (the content of which was significantly lower at stages I-II CRC than those in the control) and the levels of α-linolenic, eicosapentaenoic, docosapentaenoic, docosahexaenoic, the amount of omega-3 Fa, EPA + DHA, docodienic, dihomo-γ-linolenic, docatetraenoic fatty acids (the content of which was significantly higher in colorectal cancer than those in healthy subjects) were the most discriminating parameters in distinguishing patients with I-II stage CRC and healthy individuals. in the blood serum, the level of biomarkers had the following fatty acids: arachidonic, myristic, docosahexaenoic, the amount of omega 3 puFa, the ratio of omega 6/omega 3 puFa, pentadecanoic, docosapentaenoic, and docodiene. a model that included a list of fatty acids, such as С14:0, С15:0, С16:1;7, С18:3 n-3, C20:2 n-6, C20:3 n-6, C20:5 n-3, C22:4 n-6, C22:5 n-3, C22:6 n-3, sum of omega-3, omega-3 (EPA + DHA), and saturated / polyunsaturated fatty acids ratio provided auc 0,916 with a specificity of 0,90 and sensitivity of 0,95 in distinguishing patients with stage I-II CRC from healthy individuals.

Conclusion. the study of the levels and ratios of fatty acids in erythrocyte membranes and blood serum should be considered a promising trend in the search for biomarkers for the early diagnosis of colorectal cancer.

ONCOLOGY PRACTICE

81-87 561
Abstract

Over the past decade, stomach cancer continues to be one of the most common diseases in the world. Currently, the methods of conservative and surgical treatment of this disease are fairly standardized. However, the issue of postoperative management of patients, including the timing of the start of oral nutrition after surgery still remains debatable. In addition, modern methods of treatment are based on the use of protocols for enhanced recovery after surgery, the safety of which remains controversial and requires discussion.

Study object was to explore the safety and benefits of early oral nutrition among patients who have undergone gastrectomy for stomach cancer.

Material and methods. The authors present their own experience of nutritional support for patients who underwent gastrectomy. The study included 82 patients with locally advanced stomach cancer who received surgical treatment at the n.i. Pirogov clinic of high medical technologies in the period from 2016 to 2019.

Results. The safety and positive effect of the use of early oral feeding was proved. It was associated with shorter first exhaust time (2.8 ± 1.0 days vs 3.9 ± 1.2 days, p=0.001), shorter postoperative length of stay in the hospital (5.4 ± 1.5 days vs 9.5 ± 2.3 days; p=0.001), as well as a more dynamic recovery of laboratory parameters.

Conclusion. Early per oral nutrition after gastrectomy can reduce the length of hospital stay without increasing the incidence of concomitant complications, which indicates its safety, expediency and potential benefit for patients with gastric cancer.

88-95 595
Abstract

Background. Reconstruction of defects following surgery for head and neck cancer possess challenges for surgeons. The choice of the reconstruction option is determined by various factors, namely: the size and location of the defect, patients’ age, concomitant pathology, prognosis of the disease, and individual decisions of surgeons and patients. Microvascular surgery is a highly successful and relatively safe method for the reconstruction of large head and neck defects. However, the use of revascularized autografts is not possible in all categories of patients, and therefore the search for new reconstruction techniques is necessary to improve functional, aesthetic results and reduce trauma.

Material and methods. The use of different types of facial artery mucous-muscular (FAMM) flaps for the reconstruction of oral cavity defects after tumor resection was analyzed. From June 2020 to march 2021, 7 patients with histologically verified t2–4N0–1 oral cancer were treated at Blokhin National medical Research center of oncology (Moscow). The patients underwent tumor resection with one-stage reconstruction using different types of FAMM flaps. All patients underwent adjuvant radiation therapy.

Results. When cutting out the flap, an additional skin incision was not performed, the defect in the oral cavity was replaced by tissues of the same composition while preserving the small salivary glands, respectively, there was no hair growth and a defect in the donor bed. None of the cases had malnutrition of the flap.

Conclusion. Good functional and cosmetic results in patients who underwent FAMM flap reconstruction may set a new standard in the replacement of small-to medium-size soft tissue defects in the oral cavity

REVIEWS

96-108 483
Abstract

Purpose: to conducted a systematic analysis of data available in the current literature, modern diagnostic
algorithms, prognostic factors, survival and options for surgical treatment of metastases in the spine and
long bones of the extremities.

Material And Methods. The review included data from randomized clinical trials evaluating various diagnostic algorithms for detecting bone metastases, the frequency of metastases to the vertebral column and long bones, their number, and options for surgical or radiation treatment published over the past 10 years. The review also evaluated various prognostic factors that can be used to determine the patient’s life expectancy.

Results. Diagnostic algorithms and scales that help choose treatment strategy, taking into account prognostic factors, were published. The treatment outcomes in patients with spine and long bone metastases were shown to be improved due to personalized surgical treatment strategies.

Conclusion. Further studies are needed to identify new prognostic factors determining the oncological outcomes in patients with bone metastases. This will lead to the optimization of surgical treatment methods and the development of new algorithms for choosing the extent of surgery in patients with bone metastases.

109-117 471
Abstract

The aim of the study. to analyse possible markers of an effective antitumor cellular immune response.

Material and methods. using the keywords «checkpoint inhibitors, immunotherapy, t-lymphocytes, exhausted t-lymphocytes, anti-tumor immune response», review and original articles (n=34) published from 2005 to 2020 in the Pubmed, Web Of Science, Elsevier databases were selected.

Results. the study revealed possible markers reflecting a high activity of an adaptive immune response based on effective recognition of tumor antigens through MHC molecules, a sufficient number of T-lymphocytes and a predominance of T-cytotoxic cells, as well as a low level of expression of inhibitory receptors and small molecules. the presence of single nucleotide polymorphisms in the HLA-I and HLA-II genes encoding MHC-I and MHC-II proteins, respectively, a high level of lymphocytes, among which the most important is the predominance of CD8+ t cells and a low level of T-regulatory cells (T-reg), as well as the presence of single nucleotide polymorphisms in the genes encoding FcγR receptors of T-lymphocytes showed their predictive significance. the diagnostic significance of determining the expression of inhibitory receptors for T-lymphocytes (TIM3, LAG3, TIGIT), especially in combination with the determination of PD-1 expression, was also revealed.

Conclusion. the results obtained may be relevant for applying new methods for the assessment of the functional activity of the T-cell immune response before starting therapy with checkpoint inhibitors, as well as for the development of new diagnostic panels, which may be of interest to employees of clinical diagnostic laboratories and research centers.

118-129 671
Abstract

The purpose of the study was to identify and analyze the potential of immunotherapy aimed at enhancing the immune system’s ability to resist tumor development and (or) weakening the ability of the tumor to maintain its growth.

Material and methods. A search for available literature sources published in Medline, Pubmed, etc. Databases was made. We found 215 publications regarding the study of the formation of antitumor mechanisms, of which 57 were included in this review.

Results. The review was devoted to the analysis of the literature on tumor growth suppression by modulating inflammation, correcting the concentration of factors and enzymes, inhibiting the formation of immunosuppressive cells, enhancing antibody cytotoxicity, and stimulating cellular cytotoxicity. The feasibilities of antitumor vaccination were evaluated.

Conclusion. Different immunotherapeutic effects were found can enhance the antitumor effect of each other. In the early stages of the disease, immunotherapy can eliminate tumor cells remaining in the body after surgical removal of the primary tumor. In the advanced stages of the disease, combined treatment, including traditional cytoreductive and immunotherapeutic treatment, should be aimed at inhibiting the development of the disease. The prognosis of the disease can be assessed on an inflammatory scale based on the determination of 3 blood parameters: the content of c-reactive protein, the level of lactate dehydrogenase, and the determination of the neutrophil-lymphocyte ratio.

130-142 637
Abstract

The purpose of the study was to present up-to-date data on the frequency and significance of a number of p53-responsive oncosuppressive micrornas genes methylation in malignant neoplasms of the blood system.

Material and methods. The search for available literary sources published in the Pubmed and RISC databases was carried out. A total of 399 articles were found, of which 62 were included in this review.

Results. The p53 protein regulates a whole class of microRNAs – highly conserved small RNA molecules that affect gene expression mainly by suppressing translation. МicroRNAs play an important role in all cellular processes and can have both oncosuppressive and pro-oncogenic properties. Impaired expression of p53-activated oncosuppressive micrornas in various tumors may be associated with specific epigenetic mechanisms (DNA methylation and histone deacetylation). The review examines the molecular and genetic characteristics of oncosuppressive micrornas functioning in normal hematopoiesis, the violation of expression of which is shown in the development of hemoblastoses, namely: miR-34a, miR-34b/c, miR-145, miR-143 and miR-203. It is known that the transcription of the genes of these microRNAs is carried out and regulated from their own promoters. The latest published research results on the diagnostic, prognostic and clinical significance of gene methylation of the microRNAs under consideration in malignant neoplasms of the blood system are presented. According to literature data, common targets for mir-34a, mir-34b/c, mir-145, mir-143 and miR-203 microRNAs are mRNAs of a number of pro-oncogenes, namely: transcription factor C-MYC, positive cell cycle regulators at the G1/S transition point of CDK4, CDK6 and CYCLIN-D1 phases, anti-apoptotic proteins MDM2, MDM4, BCL2 and MCL1, as well as DNMT3A and DNMT3B methyltransferases and other molecules. In this regard, it should be noted that there are positive feedbacks between p53 and microRNAs activated by it, as well as negative feedbacks between p53-responsive micrornas and C-MYC and DNA methyltransferases.

Conclusion. Thus, the data presented in the review clarify the current understanding of the work of the regulatory network of the p53 protein and the micrornas activated by it, and also emphasize the functional association of p53-responsive microRNAs.

143-149 394
Abstract

Purpose of the study to summarize available data on methods for creating bladder cancer models for their application in preclinical studies.

Material and methods. A systematic literature search was conducted in the Elibrary, Pubmed, Googlescholar, CyberLeninka databases.

Results. The review shows current data on various bladder cancer models and their application in practice. Bladder cancer pathology, identification of diagnostic markers and the development of new therapies are of the main challenges facing the management of bladder cancer. To solve these problems, it is often necessary to conduct preclinical studies using experimental models.

Conclusion. Bladder cancer models that can fully reproduce a human disease in terms of histology and behavior are necessary to study the factors involved in cancer development, progression and metastasis. For this, various experimental models are currently used. Human tumor xenografts in mice are widely used. They can reproduce the main pathophysiological features of cancer biology. However, it is necessary to clearly present all the pros and cons of the selected experimental models. The literature review presents modern data on the etiology of bladder cancer, results of preclinical studies on various experimental models, including orthotopic and heterotopic xenografts.

CASE REPORTS

150-155 769
Abstract

Hepatoid adenocarcinoma is a rare type of adenocarcinoma with hepatocellular differention, which is characterized by early metastatic spread and poor prognosis. The treatment strategy in not clearly defined due to an extreme rarity of the tumor. Surgery is the most effective tool as a part of multimodality concept. So far, only 51 cases have been described in the literature, and only one in Russia.

Clinical case description. We report a case of metastatic hepatoid adenocarcinoma of the lung in a 54-year-old male patient. The difficulties in morphologic differential diagnosis between adenocarcinoma of the lung and primary liver cancer were described. The strategy for managing patients with hepatoid adenocarcinoma of the lung was demonstrated.

Conclusion. Hepatoid adenocarcinoma of the lung is a rare tumor with unfavourable outcome.

156-159 517
Abstract

Background. Esophageal adenocarcinoma is often diagnosed at an advanced stage. The overall five-year survival rate of metastatic esophageal adenocarcinoma is less than 15 %. The main treatment strategy is drug therapy. The search for new drugs is still ongoing. Therefore, the assessment of the effectiveness of currently existing options is of great significance.

Description of the clinical case. A 45-year-old patient with advanced esophageal cancer with omental, mediastinal and subclavian lymph node metastases received 4 cycles of CF chemotherapy and 3 cycles of DCF + trastuzumab chemotherapy. After 25 cycles of maintenance therapy with trastuzumab, stable disease was observed. There were no significant adverse events associated with the use of trastuzumab. Currently, the patient has no any symptoms of disease.

Conclusion. Trastuzumab for the treatment of HER2- overexpressing esophageal cancer was shown to be very effective. The presented clinical case demonstrates not only the feasibility of controlling metastatic disease using targeted therapy, but also maintaining a high level of quality of life.

160-166 1129
Abstract

Background. In 1–2 % of cases, burn scars can cause more aggressive skin cancer that has a worse prognosis than conventional skin cancer. Most burn scar carcinomas are the squamous cell type (88 %) with the frequency of metastasis of 27 %. Due to the rarity of this malignancy and absence of guidance, treatment of scar carcinoma continues to be controversial. Surgical excision remains a standard mode of treatment for squamous cell carcinoma of the skin. Surgery is associated with problems to define a required limit to achieve clear margins; and subsequent grafting of the postoperative defect is limited due to the rigidity of the surrounding tissue and microcirculatory defects.

Case description. We present a case report of squamous cell carcinoma of the skin originating from burn scars. The patient received a radical course of conformal external beam therapy with a total dose of of 68 Gy in 2 Gy single doses (34 fractions) resulting in an increase in the ulcer due to the destruction of the infiltrative component of the tumor. Radical electrosurgical excision of the tumor with a free TRAM-flap reconstruction in the MS-0 version (using the full width of the rectus abdominis muscle) was performed. Microvascular anastomoses were made between the deep lower epigastric and thoracodorsal vessels on the right. There were no postoperative complications. No evidence of recurrence and tumor progression was found with a follow-up for 7 months.

Conclusion. A personified approach to the treatment of burn scar carcinoma demonstrated good treatment outcomes. Surgical reconstruction of the postoperative defect in these patients may require the use of composite flaps and, in specific cases, microsurgical techniques.

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ISSN 1814-4861 (Print)
ISSN 2312-3168 (Online)