The Clinical and Genetic Landscape of Hereditary Cancer: Experience from a Single Clinical Diagnostic Laboratory.

BACKGROUND/AIM: The application of next-generation sequencing (NGS) technology in the genetic investigation of hereditary cancer is important for clinical surveillance, therapeutic approach, and reducing the risk of developing new malignancies. The aim of the study was to explore genetic predisposition in individuals referred for hereditary cancer. MATERIALS AND METHODS: A total of 8,261 individuals were referred for multigene genetic testing, during the period 2020-2023, in the laboratory, and underwent multigene genetic testing using NGS. Among the examined individuals, 56.17% were diagnosed with breast cancer, 6.77% with ovarian cancer, 2.88% with colorectal cancer, 1.91% with prostate cancer, 6.43% were healthy with a significant family history of cancer, while 3.06% had a different type of cancer and 0.21% had not provided any information. Additionally, in 85 women with breast cancer we performed whole exome sequencing analysis. RESULTS: 20% of the examined individuals carried a pathogenic variant. Specifically, 54.8% of the patients had a pathogenic variant in a clinically significant gene (BRCA1, BRCA2, PALB2, RAD51C, PMS2, CDKN2A, MLH1, MSH2, TP53, MSH6, APC, RAD51D, PTEN, RET, CDH1, MEN1, and VHL). Among the different types of pathogenic variants detected, a significant percentage (6.52%) represented copy number variation (CNV). With WES analysis, the following findings were detected: CTC1: c.880C>T, p.(Gln294*); MLH3: c.405del, p.(Asp136Metfs*2), PPM1D: c.1426_1430del, p.(Glu476Leufs*3), and SDHB: c.395A>G, p.(His132Arg). CONCLUSION: Comprehensive multigene genetic testing is necessary for appropriate clinical management of pathogenic variants' carriers. Additionally, the information obtained is important for determining the risk of malignancy development in family members of the examined individuals.

Polygenic Risk Score (PRS) Combined with NGS Panel Testing Increases Accuracy in Hereditary Breast Cancer Risk Estimation.

Breast cancer (BC) is the most prominent tumor type among women, accounting for 32% of newly diagnosed cancer cases. BC risk factors include inherited germline pathogenic gene variants and family history of disease. However, the etiology of the disease remains occult in most cases. Therefore, in the absence of high-risk factors, a polygenic basis has been suggested to contribute to susceptibility. This information is utilized to calculate the Polygenic Risk Score (PRS) which is indicative of BC risk. This study aimed to evaluate retrospectively the clinical usefulness of PRS integration in BC risk calculation, utilizing a group of patients who have already been diagnosed with BC. The study comprised 105 breast cancer patients with hereditary genetic analysis results obtained by NGS. The selection included all testing results: high-risk gene-positive, intermediate/low-risk gene-positive, and negative. PRS results were obtained from an external laboratory (Allelica). PRS-based BC risk was computed both with and without considering additional risk factors, including gene status and family history. A significantly different PRS percentile distribution consistent with higher BC risk was observed in our cohort compared to the general population. Higher PRS-based BC risks were detected in younger patients and in those with FH of cancers. Among patients with a pathogenic germline variant detected, reduced PRS values were observed, while the BC risk was mainly determined by a monogenic etiology. Upon comprehensive analysis encompassing FH, gene status, and PRS, it was determined that 41.90% (44/105) of the patients demonstrated an elevated susceptibility for BC. Moreover, 63.63% of the patients with FH of BC and without an inherited pathogenic genetic variant detected showed increased BC risk by incorporating the PRS result. Our results indicate a major utility of PRS calculation in women with FH in the absence of a monogenic etiology detected by NGS. By combining high-risk strategies, such as inherited disease analysis, with low-risk screening strategies, such as FH and PRS, breast cancer risk stratification can be improved. This would facilitate the development of more effective preventive measures and optimize the allocation of healthcare resources.

An Ectopic External Jugular Vein Draining into the Axillary Vein: a Rare Anatomical Variation with Clinical Implications.

OBJECTIVE: The external jugular vein drains a considerable part of the head and neck and constitutes a vessel implicated in various procedures in the cervical region. The aim of this study is to present an uncommon anatomical variation of the external jugular vein, and discuss the clinical implications of its presence. CASE REPORT: We present a rare case of an ectopic external jugular vein terminating into the axillary vein, that we came across during routine dissection of a male cadaver of Greek origin. CONCLUSION: The venous system of the external jugular vein is used during procedures for the treatment of various conditions such as cardiac arrhythmias, hydrocephalus and defects of the head and neck. Hence, encountering the unpredictable course of a variant draining into the axillary vein may complicate these interventions, leading to multiple manipulations and undesirable results. Surgeons should be aware of the alternate anatomy of the venous system of the cervical region, and mindful of the possibility of encountering them.

Trochlea Dysplasia as the Major Anatomic Risk Factors for Patellofemoral Joint Instability: An Infographic as a Visual Learning Tool.

Patellofemoral instability (PFI) is a common condition in children and adolescents, ranging from mild discomfort and mal-tracking to lateral patellar dislocation [1]. A number of anatomical risk factors have been described in the literature, such as trochlear dysplasia, patella alta, excessive tibial tuberosity to trochlear groove (TT-TG) distance, patellar tilt and soft tissue alterations [2]. Among them, TD has been identified as the main anatomical risk factor with the strongest association with PFI [1, 2]. In the study by Dejour et al. [2] radiographically observed TD was identified in 96% of patients with a history of patellofemoral dislocation [1, 2]. Patients with Dejour Type D dysplasia are characterized by a prominent and convex lateral facet with a vertical connection to a hypoplastic medial facet (Figure 1), which provides inadequate tracking of the patella in the trochlea during flexion leading to patella subluxation [2]. Non-operative treatment of lateral patellar dislocation presents a rate of re-dislocation up to 70% within 24 months of the first episode [3]. Sulcus deepening trochleoplasty is indicated for Type B and D dysplasia, in order to improve patella tracking, reduce the rate of re-dislocation and achieve good functional outcomes [2, 4]. Trochlea dysplasia is defined as a shallow or flattened groove with decreased resistance to lateral patellar translation. TD can be assessed on computed tomography (CT) and magnetic resonance imaging (MRI) with the use of overlapping axial images and are able to show perfectly the global shape of the femoral trochlea [2]. The thresholds for identifying trochlear dysplasia are established based on the sulcus angle ≥ 145°, medial/lateral trochlea facet asymmetry < 40%, trochlear depth < 3 mm and lateral trochlear inclination ≤ 11° and therefore it can be used in young adolescents [4, 5]. A deep knowledge of anatomic variations and abnormalities of the patellofemoral joint, which may predispose to PFI, is crucial in order to choose the appropriate treatment for each patient.

Use of photogrammetry-based digital models in anatomy education: An overview.

PURPOSE: Photogrammetry is a technique which includes taking multiple digital photographs from various angles and using those photographs to create three-dimensional virtual models. We aimed to review the outcomes of the implementation of photogrammetry in anatomy education. METHODS: We searched PubMed, Scopus and Cochrane library for studies with purpose to explore the outcomes of the use of photogrammetry-based digital models in anatomy teaching. From each included paper we extracted: authors, number of participants, anatomical region of interest, educational outcomes, and their level according to Kirkpatrick hierarchy. RESULTS: Seven studies were included. Four of them concerned neuroanatomy and three of them concerned other systems. All studies comprised participants' perceptions about the educational intervention, while two of them also evaluated anatomical knowledge acquisition. Overall, the participants rated photogrammetry-based models very highly and preferred them to other teaching tools. These models were also shown able to significantly enhance the anatomical knowledge. CONCLUSIONS: Photogrammetry-based digital objects seem to have a promising anatomy teaching potential. The value of these objects seems to be especially pertinent in teaching the relatively complex field of neuroanatomy. Further research may investigate the effectiveness of photogrammetry-based models in comparison with other anatomy education tools, and with other methods of creation of three-dimensional virtual objects.

A Rare Inflammatory Myofibroblastic Tumor of the Spleen: A Case Report.

BACKGROUND/AIM: Inflammatory myofibroblastic tumors (IMTs) are rare, solid, potentially malignant lesions of uncertain etiology. Histologically, IMTs exhibit a combination of lymphocytes and inflammatory cells within a fibroblastic myxoid layer. The diagnosis of IMTs poses a challenge for various medical specialties, including surgeons, pathologists, and oncologists, due to their non-specific clinical presentation. Furthermore, radiologists face difficulties in interpreting computed tomography (CT) or magnetic resonance imaging (MRI) results, which often yield polymorphic and inconclusive findings. Ultimately, histopathologists play a crucial role in reaching a definitive diagnosis based on the tumor's histological characteristics. They are detected in every system of the human body, most commonly in the lungs. Here, we report an uncommon occurrence of IMT in the spleen of a patient with nonspecific abdominal pain. CASE REPORT: A 56-year-old Caucasian female presented to Konstantopouleio General Hospital of Nea Ionia, Athens, Greece, with abdominal pain and discomfort. The patient had no significant medical history and normal laboratory tests. An abdominal CT revealed a large mass in the spleen. A splenectomy was performed. Histopathological analysis of the tumor revealed IMTS. CONCLUSION: Splenic IMT is a rare benign tumor with moderate malignant potential. It lacks a distinct clinical presentation and is typically identified either incidentally or during the examination of abdominal pain.

Entrapment of the Subscapular Artery between the Radial Nerve and the Posterior Wall of the Axilla: An Anatomical Variation with Clinical Significance.

OBJECTIVE: The subscapular artery vascularizes a substantial region of the thoracic wall, and the significance of its distribution is well depicted in the diversity of reconstructive procedures that rely on its blood supply. The aim of this study is to present an uncommon anatomical variation of the artery and discuss the clinical implications of its presence. CASE REPORT: This case report depicts a rare variant of compression and the kinking of the subscapular artery by the radial nerve on the posterior wall of the axilla that was encountered during dissection of a male cadaver of Greek origin. CONCLUSION: The use of autologous tissues in the reconstruction of defects and treatment of lymphedema is expanding, so the need to establish safer surgical dissections is also becoming more apparent. The case of entrapment of the subscapular artery by the radial nerve is extremely rare, however, utilizing tissues perfused by this artery for reconstructive purposes could potentially be futile and unsuccessful due to the inadequate blood supply or vessel thrombosis. Hence, the surgeon should adapt the treatment plan according to preoperative findings, as the presence of anatomical variants should always be suspected.

George Sclavunos (1869-1954): Anatomical Insights and His Contribution into the "Magenstrasse of Waldeyer".

The purpose of this article is to present a well-known physician and highlight his contribution into an essential, but neglected anatomical feature. George Sclavunos (1869-1954) was a 20th century Greek physician, whose scientific work was a significant milestone in global medical knowledge. In 1899 he became Professor of Anatomy and Head Director of the Department of Anatomy. In 1906 Sclavunos G. published the first volume of the three volume book "Human Anatomy" (1906-1926), which is characterized by its unparalleled illustrations. For more than a century it was the most important book of medical literature in Greece. In 1926 he became a Full Member of the Academy of Athens and was named Life Partner of the International Anatomical Society. His interests included Anatomy, Physiology, Histology, as well as Osteology and Syndesmology. In his book "Human Anatomy", he described for first time the "Sialine Groove of the Stomach", which was described by Waldeyer-Hartz almost at the same time as the "Magenstrasse", a German word that means "stomach road". It is a ribbon-like path that extends along the lesser curvature of the stomach from the gastric cardia to the antrum and releases the gastric content directly into the small intestine. Its importance is confirmed by its association not only with drug delivery, but also with anti-obesity surgical techniques. The old German term has come back into common medical usage in view of the commonly performed Magenstrasse and Mill procedure, a form of bariatric surgery. CONCLUSION: Sclavunos G. managed to observe an anatomical structure that has remained of great importance until today.

Keystone Flap Type IV in Breast Reconstruction: A Case Report.

OBJECTIVE: The objective of this paper is to present and document a specific case of breast reconstruction using an adapted Type IV Keystone Flap technique, with a droplet-shaped design with a reduced flap ratio, and to identify the qualities of this method. CASE REPORT: A 41-year-old woman, with a history of myocardial infarction and low ejection fraction, underwent a lumpectomy, resulting in a lower medial quadrant deficit in her left breast. After she developed skin and tissue necrosis and infection, implementing the Type IV Keystone Flap effectively addressed the deficit, ensuring sufficient coverage. The flap extended dropwise beneath the deficit, progressing anteriorly towards the upper rectus abdominis, with a ratio of 2.5:1. The flap's novel droplet shape allowed for the utilization of fewer perforators, while ensuring adequate blood supply and tissue coverage, leading to improved perfusion and aesthetic outcome. CONCLUSION: The application of the adapted Type IV Keystone Flap highlights its capacity as a versatile and effective method for breast reconstruction post-lumpectomy. With the advantages of a short learning curve, easy execution, and acceptable risk profile, it offers a valuable alternative for patients who may not be suitable for more complex surgeries. Further research is recommended to confirm its broader applicability and to conduct a comparative analysis with other techniques.

Anatomic Risk Factors for Patellofemoral Joint Instability: An Infographic as a Visual Learning Tool.

Patellofemoral instability is a complex pathology with multiple risk factors, which affects mostly young females and may avert them from both activities of daily living and sports participation. Risk factors for instability include patella alta, trochlea dysplasia, abnormal lateral patellar tilt, and increased tibial tuberosity-trochlea groove distance. The knowledge of these anatomical abnormalities is the key to identifying the problem and succeeding in treating the patients.

Aberrant accessory abductor digiti minimi manus muscle: a rare anatomical variation.

The hypothenar muscle with the greatest frequency of variations is the abductor digiti minimi manus. Except for morphological variations of this muscle, have also been reported cases of an extra wrist muscle, the accessory abductor digiti minimi manus muscle. This case report presents a rare case of an accessory abductor digiti minimi muscle characterized by an unusual origin from the tendons of the flexor digitorum superficialis. This anatomical variation was identified on a formalin - fixed male cadaver of Greek origin during routine dissection. This anatomical variation, which may result in Guyon's canal syndrome or complicate common wrist and hand surgical procedures such as the carpal tunnel release, should be known to orthopaedic surgeons and hand surgeons in particular.

Carotid Body Tumor in a 26-Year-Old Male Patient Managed With Preoperative Embolization.

Carotid body tumors are rare, highly vascularized neuroendocrine tumors that arise near the bifurcation of the common carotid artery (CCA). Controversy exists in the management of those tumors about whether preoperative embolization facilitates surgical excision and decreases perioperative complication risk. We present the case of a 26-year-old patient with a carotid body tumor manifesting as a painless pulsatile mass in the anterior triangle over the left side of the neck and provide details of the preoperative diagnostic steps. Treatment included preoperative embolization of the tumor followed by surgical excision after 48 hours to safely address this rare pathology, resulting in a favorable outcome for the patient.

A Review of the Typical Course of the Musculocutaneous Nerve into the Coracobrachialis Muscle: Its Variability and Possible Clinical Implications.

OBJECTIVE: This literature review highlights the prevalence of the typical course of the musculocutaneous nerve (MCN) through the coracobrachialis muscle (CB), and evaluates the distance from the entrance point of the MCN to the CB, taking the coracoid process (CP) as a landmark. METHODS: PubMed (MEDLINE), Scopus, and CINAHL online databases were searched in December 2022 for studies reporting the prevalence of the MCN's typical course and the distance between the CP and the MCN entrance point to the CB. RESULTS: Twenty-eight studies were included (including 2846 subjects) investigating the MCN's typical course, and eliciting a prevalence of 93.4%. The mean distance of the CP to the entrance point of the MCN's main trunk into the CB was 5.6±2cm (median 6.1cm, in 550 subjects). In 76.12% of cases the MCN's accessory branches entered the CB proximally to the MCN's main trunk. The mean distance from the CP to the entrance point of the MCN's proximal branches to the CB was 3.8±1.2cm (median 3.7cm, in 140 subjects). CONLCUSION: In the vast majority of cases, the MCN had a typical course through the CB. In cases of altered anatomy, the MCN was either absent or passed medially to the CB (without piercing it). The average entrance point of the MCN into the CB from the CP is 5.6 cm. Proximal motor branches of the MCN to the CB are common and usually arise at a mean distance of 3.8cm from the inferior border of the tip of the CP. Surgeons should be aware of both the MCN's typical and its atypical course and these distances to avoid possible complications when operating in the area.

Anatomical Variations in the Celiac Trunk: A Short Review.

OBJECTIVE: The objective of the current study was the examination of possible variants of the celiac trunk. METHODS: An advanced review of the literature search was undertaken by means of the PubMed database and Google Scholar, searching for new studies published up to October 2022. Additional articles provided useful information in relation to the aim of this review. Hence, articles that met the inclusion criteria were included in this review and the collected data were organized into a table. RESULTS: The search of the literature retrieved 10 articles that referred to the anatomical variations of the celiac trunk. According to the available literature, the most common anatomical variations are: hepatosplenic trunk where the left gastric artery originates from the abdominal aorta, hepatosplenic trunk, where the left gastric artery originates from the splenic artery, and hepatogastric trunk and splenic artery origin from the superior mesenteric artery. Many other anatomical variations of the celiac trunk may exist, such as tetrafurcation, pentafurcation and hexafurcation, that refer to the division of the celiac trunk into four, five or six branches, respectively, and should be reported as they can affect surgical approaches and the development of the appropriate treatment strategy in patients. CONCLUSION: Every visceral surgeon, interventional radiologist and abdominal imager should be familiar with these variants.

Prevalence of Axillary Artery Variants and Their Clinical Significance: A Scoping Review.

Axillary artery (AA) variants occurred quite commonly, presenting clinical implications. A literature search yielded 523 results from which 13 parameters were extracted. Some of the AA variants found were the fusion of two or more branches into common trunks, like the fusion of anterior and posterior circumflex humeral arteries. Moreover, several branches were found to emerge from different points than expected, like the lateral thoracic artery's origin from the subscapular artery instead of the second part of the AA. The importance of the knowledge of the AA variations in clinical practice is undeniable and very useful when planning interventional procedures, as in the case of AA aneurysm treatment or in cases of fracture of the surgical neck of the humerus. The heterogeneity of data limited the possibility of a quantitative summary of data. Therefore, a more systemic study of AA variants based on the origin, course, and branching pattern is suggested. The aim of the current review is to summarize current data literature regarding the AA typical anatomy and its variants, with a focus on their prevalence and possible clinical implications.

A Simplified Three-Layered Suturing Training Pad for Undergraduate Medical Students: A Technical Note.

Surgical training is a long process that requires a lot of commitment and effort. Basic surgical techniques are the foundation of every procedure, with suturing being one of them. Hence, it is of great importance for aspiring young surgeons to practice and develop their suturing skills. Quite many kinds of suturing training models have been used and proposed worldwide, ranging from commercial silicone pads to meat leftovers and various fruits. We have developed our own, simplified, and low-cost suturing training pad that consists of three layers and is based on the combined use of silicone sponge sheet and polyurethane foam. It is quite durable and elastic and has been applied in three suturing training workshops so far. For this reason, we would like to present our experience of a low-cost but effective way of promoting and achieving further surgical excellence.

Fusion of the Median and Musculocutaneous Nerves Masquerading as Biceps' Innervation from the Median Nerve.

Embryologically, the musculocutaneous nerve (MCN) comes from the lateral root of the median nerve, and thus numerous anatomical variations concerning the formation and branching pattern of these two nerves of the brachial plexus have been described. In this case study, we describe a relatively uncommon case of fusion of the median and MCNs that was identified during routine teaching dissection of a male human cadaver. The identification of this anatomical variation requires awareness of the embryological background, as it may be confused with biceps innervation from the median nerve or the existence of a communicating branch between the two nerves. In addition, awareness of such anatomical variations is of undisputable significance for the safety of surgical operations in the brachial plexus and the arm in general.