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The purpose of this study was to determine the prevalence and to investigate the morphology of the sulcus of the caudate process in a Greek population, along with a systematic review and meta-analysis of the literature. Overall, 103 consecutive patients undergoing laparoscopic cholecystectomy were included in the analysis. The sulcus was present in 91% and three morphological variants were identified (groove 69%, slit 21% and scar 10%). The sulcus had a horizontal course in 90% of patients and a mean length of 25 ± 13 mm. The meta-analysis included 27 surgical and 11 cadaveric studies with 6661 cases in total. The pooled prevalence of the sulcus was 80% and did not differ significantly among various geographical regions. Concerning sulcus subtypes, the binary "open/fused" classification was used to unify the heterogeneous data. The "open" type was more frequent than the "fused" (64.5% vs 35.5%). A horizontal course was observed in 53.5% and an oblique in 45.7%. The sulcus contained the right portal pedicle in 38%, the right posterior portal pedicle in 37%, and the right posteroinferior pedicle in 23.5%. In conclusion, the sulcus of the caudate process is a very helpful anatomical landmark in hepatectomy and laparoscopic cholecystectomy and can be identified in the majority of patients. However, various classifications for the morphological variants and diverse terminology cause discrepancy in the literature and create the need for a single classification system. The proposed 3-tier classification (groove, slit, scar) is simple and easy to remember and avoids ambiguous nomenclature.

Gut microbial dysbiosis and microbial passage into the peripheral blood leads to colorectal cancer (CRC) and disease progression. Toll-like (

Protrusion of the appendix within an inguinal hernia is termed an Amyand’s hernia. A systematic review of case reports and case series of Amyand’s hernia was performed, with emphasis on surgical decision-making. The English literature (2000–2019) was reviewed, using PubMed and Embase, combining the terms “hernia”, “inguinal”, “appendix”, “appendicitis” and “Amyand”. Overall, 231 studies were included, describing 442 patients. Mean age of patients was 34 ± 32 years (adults 57.5%, children 42.5%). 91% were males, while a left-sided Amyand’s hernia was observed in 9.5%. Of 156 elective hernia repairs, 38.5% underwent appendectomy and 61.5% simple reduction of the appendix. 88% of the adult patients had a mesh repair, without complications. Of 281 acute cases, hernial complications (76%) and acute appendicitis (12%) were the most common preoperative surgical indications. Appendectomy was performed in 79%, more extensive operations in 8% and simple reduction in 13% of cases. A mesh was used in 19% of adult patients following any type of resection and in 81% following reduction of the appendix. Among acute cases, mortality was 1.8% and morbidity 9.2%. Surgical site infections were observed in 3.6%, all of which in patients without mesh implantation. In elective Amyand’s hernia cases, appendectomy may be considered in certain patients, provided faecal spillage is avoided, to prevent mesh infection. In cases of appendicitis, prosthetic mesh may be used, if the surgical field is relatively clean, whereas endogenous tissue repairs are preferred in cases of heavy contamination.

The splenic artery (SA) is the largest and most tortuous branch of the celiac trunk with a wide spectrum of variants, particularly in its terminal branches. The current study presents a systematic review of the English literature on the SA variations, with emphasis on its terminal branching patterns. Thirty cadaveric studies (3132 specimens) were included in the analysis. The SA originated from the celiac trunk in 97.2%, from the abdominal aorta in 2.1% and from the superior mesenteric or the common hepatic artery in 0.7% of cases. A suprapancreatic course was observed in 77.4%, retropancreatic course in 17.8%, anteropancreatic course in 3.4% and intrapancreatic course in 1.3%. In the majority of cases, the SA bifurcated into superior and inferior lobar arteries (83.4%), with trifurcation and quadrifurcation in 11.3% and 2.7%, respectively. Five or more lobar branches (1.4%) and a single lobar artery (1.2%) were rarely identified. The distributed branching pattern was found in 72.7%, whereas the magistral pattern in 26.9%. The inferior and superior polar arteries (IPA and SPA) were found in 47.7% and 41.7% of cases, respectively, while polar artery agenesis was recorded in 28.2%. The SPA usually originated from the SA main trunk (53.6%) or from the superior lobar artery (33.1%). The IPA emanated mainly from the left gastroepiploic artery (53%), from the SA (23.5%) or the inferior lobar artery (21.9%). Intersegmental anastomoses between adjacent arterial segments were identified in 14.2%. Knowledge of the SA aberrations is important for surgeons and radiologists involved in angiographic interventions.

The therapeutic approaches to cancer remain a considerable target for all scientists around the world. Although new cancer treatments are an everyday phenomenon, cancer still remains one of the leading mortality causes. Colorectal cancer (CRC) remains in this category, although patients with CRC may have better survival compared with other malignancies. Not only the tumor but also its environment, what we call the tumor microenvironment (TME), seem to contribute to cancer progression and resistance to therapy. TME consists of different molecules and cells. Cancer-associated fibroblasts are a major component. They arise from normal fibroblasts and other normal cells through various pathways. Their role seems to contribute to cancer promotion, participating in tumorigenesis, proliferation, growth, invasion, metastasis and resistance to treatment. Different markers, such as a-SMA, FAP, PDGFR-β, periostin, have been used for the detection of cancer-associated fibroblasts (CAFs). Their detection is important for two main reasons; research has shown that their existence is correlated with prognosis, and they are already under evaluation as a possible target for treatment. However, extensive research is warranted.

One of the most intriguing eras in the evolution of hernia surgery is the second half of the 18th century, when surgeons interested, also, in anatomy, started to publish studies on the abdominal wall and the inguinal canal. Petrus Camper (1722–1789), a well-known “praelector anatomiae” of the Amsterdam Guild of Surgeons and Professor of Anatomy and Surgery at the Universities of Franeker, Amsterdam, and Groningen, performed dissections on corpses of children and adults to study the anatomy and aetiology of inguinal hernias. He rejected the prevailing concept of that time that a hernia was caused by “a rupture of the peritoneum” and provided a clear description of the aetiology of hernias in both children and adults. His geometrical measurement of the pelvis and his acquired craftsmanship provided the basis for the development of an effective and reliable truss to treat inguinal hernia conservatively. His artistic and drawing talent rendered him great facility in presenting his anatomical observations of the inguinal canal in a marvelous way. Campers “Icones herniarum” include exceptional anatomical illustrations of inguinal hernias. His anatomic studies allowed the development of hernia surgery based on anatomy rather than barbaric castration by ancient “herniotomists”. Petrus Camper should be considered as a pioneer in anatomy and aetiology of inguinal hernias.

This series of 10 articles (four original articles, five literature reviews, and one systematic review) is presented by international experts in the study of microbiota and its relation to colorectal cancer (CRC) [...]

The ilioinguinal, iliohypogastric, genitofemoral, obturator, and pudendal nerves are the major sensory nerves that may be involved in chronic groin and genital pain with a significant impact on the quality of life of patients. The diagnosis remains clinical, and US-guided diagnostic injections using an anesthetic may aid in confirming the clinical suspicion. The anatomy of the peripheral nerves can be successfully studied using imaging. High-resolution ultrasound is increasingly used in the clinical setting for visualizing small peripheral nerves, and magnetic resonance imaging provides an anatomical overview of the relationship between small nerves and surrounding structures. In this pictorial assay, we review the anatomy and clinical relevance of the ilioinguinal, iliohypogastric, genitofemoral, obturator, and pudendal nerves. We summarize the various techniques for ultrasound identification, and present the ultrasound-guided infiltration techniques for injecting the ilioinguinal, iliohypogastric, genitofemoral, obturator, and pudendal nerves. Corresponding magnetic resonance images and clinical photos of the probe placement technique are provided for anatomical correlation. This paper is aimed to serve as a practical technical guide for physicians to familiarize themselves with the ultrasound anatomy of the major inguinal sensory nerves and to enable successful ultrasound identification and ultrasound-guided diagnostic or therapeutic infiltrations for pain management of the ilioinguinal, iliohypogastric, genitofemoral, obturator, and pudendal nerves.

To describe the cervical vagus nerve (CVN) topography at the thyroid lobe (TL) level using high-resolution ultrasound and to investigate the possible association with anthropometric data, TL size, and thyroid disease. We prospectively examined 550 CVNs in 275 (205 female, 70 male) individuals with normal thyroid (53/275, 19.3%), multinodular disease (167/275, 60.7%), and Hashimoto thyroiditis (55/275, 20%). The CVN location relative to the common carotid artery was recorded as typical (lateral position) and atypical (anterior, medial, and posterior position). The shortest distance between CVN and TL margin, the TL dimensions, and volume were measured. Normal thyroid subjects had lateral-positioned right CVNs in 100% and lateral/anterior/medial left CVNs in 81.1%, 15.1%, and 3.8%, respectively. CVN types did not differ significantly bilaterally between study groups. Asymmetry in CVN topography in all subjects was found in 22.2%, of which anterior CVN was the most common atypical position (64%), especially on the left side (82%). Significant gender, age, body mass, and BMI differences among CVN types were observed on the left side only. Among CVN types, no difference in TL dimensions, volume, and CVN-TL distance was found in all study groups. A weak negative correlation was recorded between CVN-thyroid distance and TL volume only on the left side (r = − 0.147, p = 0.01). Asymmetry in CVN topography is mainly due to the increased incidence of the anterior location of CVN on the left side. Age and anthropometric parameters are different on the left side possibly due to the increased prevalence of left CVN variants.

Human populations are chronically exposed to mixtures of toxic chemicals. Predicting the health effects of these mixtures require a large amount of information on the mode of action of their components. Xenobiotic metabolism by bacteria inhabiting the gastrointestinal tract has a major influence on human health. Our review aims to explore the literature for studies looking to characterize the different modes of action and outcomes of major chemical pollutants, and some components of cosmetics and food additives, on gut microbial communities in order to facilitate an estimation of their potential mixture effects. We identified good evidence that exposure to heavy metals, pesticides, nanoparticles, polycyclic aromatic hydrocarbons, dioxins, furans, polychlorinated biphenyls, and non-caloric artificial sweeteners affect the gut microbiome and which is associated with the development of metabolic, malignant, inflammatory, or immune diseases. Answering the question ‘Who is there?’ is not sufficient to define the mode of action of a toxicant in predictive modeling of mixture effects. Therefore, we recommend that new studies focus to simulate real-life exposure to diverse chemicals (toxicants, cosmetic/food additives), including as mixtures, and which combine metagenomics, metatranscriptomics and metabolomic analytical methods achieving in that way a comprehensive evaluation of effects on human health.

Highlights • Ectopic parathyroid adenomas located deeper in the mediastinum remain a surgical challenge. • Their incidence reaches up to 20% of the general population and they tend to constitute a severe cause of failed primary surgery for PHPT. • Such aberrations seem to be more common than described in the literature and there are possible anatomic aberrations that have not been described yet. • Preoperative detection of the mediastinal parathyroid adenoma and detailed exposure of the operative field are essential for a safe mid-sternal thoracotomy., Introduction Ectopic parathyroid glands occur in 6–16% of cases of PHPT and they constitute a potential cause of failed primary surgical therapy. In particular, aberrant adenomas located deeper in the mediastinum, as in the presented case, remain a severe challenge for the surgeons. Presentation of case A 54-year-old Caucasian female proceeded to our institution with signs and symptoms of PHPT. Imaging studies performed identified a large mass localized in the lower anterior mediastinum, on the left of the median line. A mid-sternal thoracotomy was performed and the aberrant adenoma was finally detected anterior to the pericardium and the left pericardiophrenic vessels and the left phrenic nerve. The operation was uneventful. A meticulous review of the literature was conducted as well. Discussion Single parathyroid adenomas are the key culprits of PHPT. Anatomic aberrations of the location of the parathyroid glands and their adenomas are more common than described in the literature and there are possible anatomic aberrations that have not been described yet. All these anatomic variations constitute major risk-factors of thoracic bleeding and of nerve injury. Conclusion Detailed preoperative detection in addition to meticulous exposure of the operative field are fundamental in order to perform a safe adenoma excision without harmful impacts to the patient.

Highlights • BCT may present anatomical variations concerning its origin and its trajectory. • Preoperative observation of these anatomical variations has vital clinical and surgical importance, since they constitute risk-factors of severe bleeding. • Fundamentals to avoid iatrogenic injury are: (1) exposure of the trajectory and the origin of BCT, since it is quite evident that probable novel anatomic variations could be unexpectedly detected during the operation (2) good haemostasis and (3) preoperative utilization of diagnostic ultrasound., Introduction The brachiocephalic trunk (BCT), also known as the “anonymous artery” constitutes the first branch of the aortic arch that bifurcates at the level of the right sternoclavicular joint into the RCCA and the RSA. Anatomical variations of the origin and the trajectory of BCT are of vital clinical significance since they constitute major risk-factors of hemorrhage when performing tracheotomy, surgeries at the anatomic area of the neck as in the presented case. Presentation of case A 64-year-old Caucasian female proceeded to our institution with signs and symptoms of PHPT. Imaging studies performed identified a large mass localized posterior to the right thyroid lobe. During the operation, surgeons incidentally detected anterior to the trachea aberrant trajectory of the BCT. The operation was uneventful. A meticulous review of the literature was conducted as well. Discussion Anatomical anomalies of the origin and the trajectory of BCT are vaguely described in the literature. However, these anatomic variations constitute major risk-factors of accidental bleeding and subsequent complications when performing surgeries of the thyroid and parathyroid glands, tracheotomy and invasive radiological interventions. Conclusion Deep knowledge of such variations of the trajectory of the BCT in addition to detailed exposure of the operative field constitute the cornerstone in order surgeons to perform a safe intervention.

Colorectal cancer (CRC) is the third most diagnosed type of cancer affecting males, and the second most diagnosed type of cancer affecting females, and one of the leading causes of cancer-related mortality globally. The estimation of the micronuclei (MN) frequency in peripheral blood lymphocytes (PBLs) from patients with CRC is proposed as a prognostic/predictive easy-to-use biomarker. In this study, we aimed to investigate the effects of systemic treatment on the MN frequency in PBLs from patients with CRC in order to determine the effectiveness of the MN frequency as a biomarker. For this purpose, from 2016 to 2018, we quantified the MN frequency as a prognostic/predictive biomarker in serial samples from 25 patients with metastatic CRC (mCRC) using cytokinesis block micronucleus assay (CBMN assay). The MN frequency in the PBLs of the patients was evaluated before, during the middle and at the end of the therapy (approximately 0, 3 and 6 months). The results revealed a common pattern regarding the fluctuation in the MN frequency. Statistical analysis confirmed that when the disease response was estimated with radiological criteria, a good response was depicted at the MN frequency and vice versa. Consequently, the findings of this study suggest that the MN frequency may serve as a promising prognostic/predictive biomarker for the monitoring of the treatment response of patients with CRC.

PurposeDue to the current practice on colorectal cancer (CRC) management, chemoresistance is most often recognized at the end of the treatment. Therefore, effective and easy-to-use prognostic biomarkers are needed.Experimental DesignWe evaluated the prognostic significance of two novel CRC biomarkers: a) micronuclei frequency (MNf) in 55 metastatic CRC (mCRC) and 21 locally advanced rectal cancer (laRC) patients using cytokinesis block micronucleus assay (CBMN assay) and b) telomerase activity (TA) in 23 mCRC and five laRC patients using TRAP-ELISA. Both biomarkers were evaluated in peripheral blood lymphocytes (PBLs) before, at the middle, and at the end of the therapy (approximately 0, 3, and 6 months) for mCRC patients before, at the end of the therapy, and after surgery for laRC patients.ResultsOverall, MNf demonstrated significant prognostic value since a decrease of MNf less than 29% between middle and initial MNf measurements can discriminate between progressive and stable/responsive disease with sensitivity of 36% and specificity of 87.0% while being able to identify responsive disease with sensitivity of 72.7% and specificity of 59.3%. On the other hand, TA presented a significant trend of increase (p = 0.07) in patients with progressive disease at the middle measurement.ConclusionsThe findings of this study suggest that the MN frequency may serve as a promising prognostic biomarker for the monitoring of the treatment response of patients with CRC, while TA should be evaluated in a larger group of patients to further validate its significance.

The knowledge of Anatomy during the Ottoman domination in Greece has not been widely studied. Medical knowledge of the time can be retrieved from folk and erudite books called Iatrosophia. The majority of these books focused on empirical diagnostics and therapeutics. However, a small quota of these Iatrosophia includes important information about anatomy. The interest in anatomy appears only after the Neohellenic Enlightenment (1750-1821) and has been associated to the scholarly background of the 1821 revolution against the Ottomans. At the same time, anatomy has been discussed by various authors in diverse contexts. All in all, it appears that a consensus on the importance of anatomy has been established among Greek scholars in the late 18th century, leading to the translation of current anatomical knowledge to the contemporary language and literature.

Protrusion of the appendix within an inguinal hernia is termed an Amyand's hernia. A systematic review of case reports and case series of Amyand's hernia was performed, with emphasis on surgical decision-making.The English literature (2000-2019) was reviewed, using PubMed and Embase, combining the terms "hernia", "inguinal", "appendix", "appendicitis" and "Amyand". Overall, 231 studies were included, describing 442 patients.Mean age of patients was 34 ± 32 years (adults 57.5%, children 42.5%). 91% were males, while a left-sided Amyand's hernia was observed in 9.5%. Of 156 elective hernia repairs, 38.5% underwent appendectomy and 61.5% simple reduction of the appendix. 88% of the adult patients had a mesh repair, without complications. Of 281 acute cases, hernial complications (76%) and acute appendicitis (12%) were the most common preoperative surgical indications. Appendectomy was performed in 79%, more extensive operations in 8% and simple reduction in 13% of cases. A mesh was used in 19% of adult patients following any type of resection and in 81% following reduction of the appendix. Among acute cases, mortality was 1.8% and morbidity 9.2%. Surgical site infections were observed in 3.6%, all of which in patients without mesh implantation.In elective Amyand's hernia cases, appendectomy may be considered in certain patients, provided faecal spillage is avoided, to prevent mesh infection. In cases of appendicitis, prosthetic mesh may be used, if the surgical field is relatively clean, whereas endogenous tissue repairs are preferred in cases of heavy contamination.

The potential renoprotective effects of vardenafil (VAR) have been evaluated in a very limited number of studies using acute kidney injury animal models other than contrast-induced nephropathy (CIN) with promising results, while avanafil (AVA) has not been evaluated in this respect before. The purpose of this study was to evaluate for the first time the potential renoprotective effect of VAR and AVA in a rat model of CIN. Twenty-five male Wistar rats were equally assigned into five groups: control, CIN, CIN+N-acetyl cysteine (NAC) (100 mg/kg/day) as a positive control, CIN+VAR (10 mg/kg/day) and CIN+AVA (50 mg/kg/day). CIN was induced by dehydration, inhibition of prostaglandin and nitric oxide synthesis as well as exposure to the contrast medium (CM). Serum Cr (sCr) levels were measured at 24 and 48 h after CIN induction. At 48 h of CM exposure, animals were sacrificed. Matrix metalloproteinase (MMP) 2 (MMP-2) and MMP-9, kidney injury molecule 1 (KIM-1) and cystatin-C (Cys-C) were measured on renal tissue. Histopathological findings were evaluated on kidney tissue. All treatment groups had close to normal kidney appearance. sCr levels subsided in all treatment groups compared to CIN group at 48 h following CIN induction. A significant decline in the levels of MMP-2, MMP-9, KIM-1 and Cys-C compared to CIN group was observed. These results provide emerging evidence that VAR and AVA may have the potential to prevent CIN.

Simple Summary Immunotherapy and immune checkpoint inhibitors have become the breakthrough treatment with extended responses and survival rates in various neoplasms. They use the immune system to defeat cancer, while gut microbiota seems to play a significant role in that attempt. To date, colorectal cancer patients have gained little benefit from immunotherapy. Only mismatch repair-deficient/microsatellite-unstable tumors seem to respond positively to immunotherapy. However, gut microbiota could be the key to expanding the use of immunotherapy to a greater range of colorectal cancer patients. In the current review study, the authors aimed to present and analyze the mechanisms of action and resistance of immunotherapy and the types of immune checkpoint inhibitors (ICIs) as well as their correlation to gut microbiota. A special reference will be made in the association of immunotherapy and gut microbiota in the colorectal cancer setting. Abstract Over the last few years, immunotherapy has been considered as a key player in the treatment of solid tumors. Immune checkpoint inhibitors (ICIs) have become the breakthrough treatment, with prolonged responses and improved survival results. ICIs use the immune system to defeat cancer by breaking the axes that allow tumors to escape immune surveillance. Innate and adaptive immunity are involved in mechanisms against tumor growth. The gut microbiome and its role in such mechanisms is a relatively new study field. The presence of a high microbial variation in the gut seems to be remarkably important for the efficacy of immunotherapy, interfering with innate immunity. Metabolic and immunity pathways are related with specific gut microbiota composition. Various studies have explored the composition of gut microbiota in correlation with the effectiveness of immunotherapy. Colorectal cancer (CRC) patients have gained little benefit from immunotherapy until now. Only mismatch repair-deficient/microsatellite-unstable tumors seem to respond positively to immunotherapy. However, gut microbiota could be the key to expanding the use of immunotherapy to a greater range of CRC patients.

Colorectal cancer (CRC) remains one of the leading causes of cancer-related death due to its high metastatic potential. This study aimed to investigate the detection and heterogeneity of circulating tumor cells (CTCs) and the microsatellite instability (MSI) status in advanced CRC patients prior to any systemic front-line treatment. Peripheral whole blood was obtained from 198 patients. CTCs were detected using double immunofluorescence and a real time-polymerase chain reaction assay, whereas MSI status was evaluated using fragment analysis. Median age of the patients was 66 years, 63.1% were males, 65.2% had a colon/sigmoid tumor location and 90.4% had a good performance status (PS). MSI-High status was detected in 4.9% of the patients, 33.3%, 56.1% and 8.6% patients had at least one detectable CEACAM5+/EpCAM+, CEACAM5+/EpCAM&minus, and CEACAM5&minus, /EpCAM+ CTC, respectively, and 9.1% of the patients had CEACAM5mRNA-positive CTCs. Following multivariate analysis, age, PS and MSI were confirmed as independent prognostic factors for decreased time to progression, whereas age, PS and CTC presence were confirmed as independent prognostic factors for decreased overall survival. In conclusion, our data support the use of CEACAM5 as a dynamic adverse prognostic CTC biomarker in patients with metastatic CRC and MSI-High is considered an unfavorable prognostic factor in metastatic CRC patient tumors.

Simple Summary The microbial communities of the intestine exist in a delicate balance with the human. Colorectal cancer is one of the most common gastrointestinal malignancies, and the microbiota seems to be related to it. The intestinal microbiota of patients after colorectal surgery is changed due to surgical stress and other perioperative factors. The occurrence of complications after colorectal cancer (CRC) surgery may depend on these bacterial shifts, which could also be associated with prognosis and survival in postoperative CRC patients. Abstract The intestinal microbiota consists of numerous microbial species that collectively interact with the host, playing a crucial role in health and disease. Colorectal cancer is well-known to be related to dysbiotic alterations in intestinal microbiota. It is evident that the microbiota is significantly affected by colorectal surgery in combination with the various perioperative interventions, mainly mechanical bowel preparation and antibiotic prophylaxis. The altered postoperative composition of intestinal microbiota could lead to an enhanced virulence, proliferation of pathogens, and diminishment of beneficial microorganisms resulting in severe complications including anastomotic leakage and surgical site infections. Moreover, the intestinal microbiota could be utilized as a possible biomarker in predicting long-term outcomes after surgical CRC treatment. Understanding the underlying mechanisms of these interactions will further support the establishment of genomic mapping of intestinal microbiota in the management of patients undergoing CRC surgery.

Skin cancer represents the most common type of cancer among Caucasians and presents in two main forms: melanoma and non-melanoma skin cancer (NMSC). NMSC is an umbrella term, under which basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and Merkel cell carcinoma (MCC) are found along with the pre-neoplastic lesions, Bowen disease (BD) and actinic keratosis (AK). Due to the mild nature of the majority of NMSC cases, research regarding their biology has attracted much less attention. Nonetheless, NMSC can bear unfavorable characteristics for the patient, such as invasiveness, local recurrence and distant metastases. In addition, late diagnosis is relatively common for a number of cases of NMSC due to the inability to recognize such cases. Recognizing the need for clinically and economically efficient modes of diagnosis, staging, and prognosis, the present review discusses the main etiological and pathological features of NMSC as well as the new and promising molecular biomarkers available including telomere length (TL), telomerase activity (TA), CpG island methylation (CIM), histone methylation and acetylation, microRNAs (miRNAs), and micronuclei frequency (MNf). The evaluation of all these aspects is important for the correct management of NMSC; therefore, the current review aims to assist future studies interested in exploring the diagnostic and prognostic potential of molecular biomarkers for these entities.

Vitamin D deficiency has been associated with increased colorectal cancer (CRC) incidence risk and mortality. Vitamin D mediates its action through the binding of the vitamin D receptor (VDR), and polymorphisms of the VDR might explain these inverse associations. The aim of the study was the investigation of the relevance of rs731236, Thermus aquaticus I (TaqI), rs7975232, Acetobacter pasteurianus sub. pasteurianus I (ApaI), rs2228570, Flavobacterium okeanokoites I (FokI) and rs1544410, Bacillus stearothermophilus I (BsmI) polymorphisms of the VDR gene to colorectal carcinogenesis (CRC) and progression. Peripheral blood was obtained from 397 patients with early operable stage II/III (n = 202) and stage IV (n = 195) CRC. Moreover, samples from 100 healthy donors and 40 patients with adenomatous polyps were also included as control groups. Genotyping in the samples from patients and controls was performed using polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP). A significant association was revealed between all four polymorphisms and cancer. Individuals with homozygous mutant (tt, aa, ff or bb) genotypes were more susceptible to the disease (p &lt, 0.001). All of the mutant genotypes detected were also significantly associated with stage IV (p &lt, 0.001), leading to significantly decreased survival (p &lt, 0.001). Moreover, all four polymorphisms were significantly associated with KRAS (Kirsten ras oncogene) mutations and Toll-like receptor (TLR2, TLR4 and TLR9) genetic variants. In multivariate analysis, tt, aa and ff genotypes emerged as independent factors associated with decreased overall survival (OS) (p = 0.001, p &lt, 0.001 and p = 0.001, respectively). The detection of higher frequencies of the VDR polymorphisms in CRC patients highlights the role of these polymorphisms in cancer development and progression.

The large intestine, part of the gastrointestinal tract (GI), is composed of all three germ layers, namely the endoderm, the mesoderm and the ectoderm, forming the epithelium, the smooth muscle layers and the enteric nervous system, respectively. Since gastrulation, these layers develop simultaneously during embryogenesis, signaling to each other continuously until adult age. Two invaginations, the anterior intestinal portal (AIP) and the caudal/posterior intestinal portal (CIP), elongate and fuse, creating the primitive gut tube, which is then patterned along the antero‑posterior (AP) axis and the radial (RAD) axis in the context of left‑right (LR) asymmetry. These events lead to the formation of three distinct regions, the foregut, midgut and hindgut. All the above‑mentioned phenomena are under strict control from various molecular pathways, which are critical for the normal intestinal development and function. Specifically, the intestinal epithelium constitutes a constantly developing tissue, deriving from the progenitor stem cells at the bottom of the intestinal crypt. Epithelial differentiation strongly depends on the crosstalk with the adjacent mesoderm. Major molecular pathways that are implicated in the embryogenesis of the large intestine include the canonical and non‑canonical wingless‑related integration site (Wnt), bone morphogenetic protein (BMP), Notch and hedgehog systems. The aberrant regulation of these pathways inevitably leads to several intestinal malformation syndromes, such as atresia, stenosis, or agangliosis. Novel theories, involving the regulation and homeostasis of intestinal stem cells, suggest an embryological basis for the pathogenesis of colorectal cancer (CRC). Thus, the present review article summarizes the diverse roles of these molecular factors in intestinal embryogenesis and related disorders.

Dysbiosis has been associated with various diseases and is of major health importance. Dysbiosis leads to microbial translocation, which is the passage of microorganisms, their fragments, or their metabolites from the intestinal lumen into the blood circulation and other sites. The aim of the study was to determine whether microbial translocation occurs in stage II/III-IV colorectal cancer (CRC) patients. The aim was also to evaluate the usefulness of blood PCR for diagnosis of such translocation and correlate the presence of toll-like receptor/vitamin D receptor (TLR/VDR) gene polymorphisms with microbial DNA fragments detected in the blood of CRC patients. Three hundred and ninety-seven CRC patients enrolled in the study. Peripheral blood DNA was analyzed using PCR for the amplification of genomic DNA encoding 16S rRNA, the &beta, galactosidase gene of Escherichia coli, glutamine synthase gene of Bacteroides fragilis, and 5.8S rRNA of Candida albicans. Significantly higher rates of all microbial fragments, but E. coli, detected were observed in the CRC patients (p &lt, 0.001), such detection of all four microbial fragments was also significantly associated with the metastatic disease (p &lt, 0.001), leading to shorter survival rates (p &lt, 0.001). Tumor location in the right colon also significantly correlated with shorter survival (p = 0.016). Individuals with homozygous mutant alleles of TLR/VDR polymorphisms had significantly higher detection rates of microbial DNA fragments. The detection of microbial DNA fragments in CRC patients highlighted the role of these microbes in cancer development, progression, and patients&rsquo, survival.

Discovery of the lymphatic system is documented in numerous sources and can be attributed to a variety of persons. Like many other important developments in medicine, the recognition of the lymphatic system starts with Hippocrates (ca. 460–370 BC), who described a disease course consistent with metastasis to lymph nodes. Until the 17th century, knowledge about the anatomy and pathophysiology of the lymphatic system was limited, probably because of the difficulty of visualizing lymph vessels in animals and humans. Frederik Ruysch (1638-1731), a “praelector anatomiae” of the Amsterdam Guild of Surgeons, must be considered one of the pioneers in lymphatic research. His contribution relied on meticulous anatomical dissection of lymph vessels, and with his innovative preservation techniques, he was the first to visualize lymphatic valves. This major step provided a better understanding of lymphatic anatomy and the circulation of lymph. The German pathologist Rudolf Virchow (1821–1902) suggested that lymph nodes function as filters in the lymphatic system and could therefore contain cancer. He was the first to propose that lymph fluid from any given area of the body drains through lymphatics to a specific lymph node and subsequently to other lymph nodes. Consequently, clinicians began to recommend that local therapy of cancer should be supplemented with regional lymph node treatment to improve the cure rate. Subsequently, lymph node surgery became an essential element of surgical oncology. Lymphatic mapping and sentinel lymph node biopsy were developed several decades ago by Donald Morton (1934–2014) to stage melanoma accurately and to avoid unnecessary lymph node dissection. In a way, history is now repeating itself, as today there is renewed interest in imaging lymph vessels and lymph nodes from an oncological perspective, more than 300 years since Ruysch committed himself to visualizing the lymphatic system. From this perspective, it is important to acknowledge early contributions of Ruysch in providing the foundations to our knowledge of lymphatic anatomy.

The Amsterdam Guild of Surgeons organized lessons in anatomy as part of the education of surgical trainees and surgeons. Appreciating that the acquisition of correct anatomical knowledge by regular perceptive education during dissection of the human body was essential for surgeons, in 1555 Philip II, King of Spain and Holland, gave his permission to the Amsterdam Guild of Surgeons to perform anatomical dissections on bodies of deceased humans. The anatomy instructors, called “praelectores anatomiae”, who were always academically educated medical doctors, were appointed by the guild for the teaching of anatomy. They commissioned painters to produce group portraits, with the “praelector anatomiae” delivering an anatomy lesson as the central figure. Probably the best-known of such paintings is the masterpiece of Rembrandt van Rijn (1632) "The anatomy lesson of Dr. Nicolaes Tulp". Although these paintings are historical portraits rather than authentic pictures of an anatomical dissection, today this series of paintings of the Amsterdam Guild of Surgeons still reminds us of this essential part of the surgical training programme. While anatomy lessons on bodies of deceased humans was already an obligatory and crucial part of the medical (i.e., surgical) education in the 16th century, nowadays many medical schools unfortunately do not provide such practical anatomy lessons for their students, for whom usually only theoretical lessons and textbooks constitute the educational tools for learning human anatomy.

Telomerase is the enzyme that maintains telomere length by adding telomeric repeats after each cell division. Numerous metabolic factors such as obesity, insulin resistance or physical inactivity have been associated with shortened telomeres. In the present study, we assessed telomerase activity in diabetic patients having or not foot ulcer. A total of 90 adult patients with type 2 diabetes mellitus (T2DM) were studied. Patients were allocated into two groups according to the absence or presence of active foot ulcers as follows: Νon-ulcer group (N=58) and ulcer group (N=32). Our data revealed that the patients with diabetic ulcers had significantly greater waist circumference and neuropathy disability score, while exhibiting lower telomerase activity, indicating the possible existence of a common clinical profile among ulcer-bearing diabetic patients. Validation of our findings by extending the study in larger patient groups may contribute to the understanding of T2DM pathophysiology and its main clinical implications.

Oxaliplatin-fluoropyrimidine combination therapy is the gold standard treatment for patients with stage III colorectal cancer (CRC), however, treatment duration is now under re-evaluation. The aim of the study was the evaluation of the non-inferiority of three over six months treatment with FOLFOX or CAPOX, in stage III CRC patients. Peripheral blood samples from 121 patients were collected, at three time points during treatment and evaluated for circulating tumor cells (CTCs) and microbial DNA detection (16S rRNA, Escherichia coli, Bacteroides fragilis,&nbsp, Candida albicans). Of all patients, 41.3% and 58.7% were treated with FOLFOX and CAPOX, respectively. CTCs were significantly decreased and increased after three and six months of treatment, respectively. CAPOX tends to reduce the CTCs after 3 months, whereas there is a statistically significant increase of CTCs in patients under FOLFOX after 6 months. A significant correlation was demonstrated between microbial DNA detection and both CTCs detection at baseline and CTCs increase between baseline and three months of treatment. To conclude, the current study provides additional evidence of non-inferiority of three over 6 months of treatment, mainly in patients under CAPOX.

The needle shaping technique can be used to perform subcutaneous microtransplants, enabling the 'lifting' of the skin. This prospective cohort study aimed to examine the effects of needle shaping on facial skin tone, volume and histological structure. A total of 54 women underwent the needle shaping procedure performed by inserting a tiny acupuncture needle combined with mixed electrical currents. The overall treatment was completed within 4 sessions of 2 months apart, once every 15 days. Maintenance was ensured by 2 sessions (no longer than 15 days apart) every 6 months. Macroscopic skin appearance was evaluated by a specialized dermatologist and the satisfaction of the patients was assessed. The microscopic structure of the skin dermis was evaluated by optic and scanning electron microscopy. I-chrome staining demonstrated more compact dermis-collagen fibers which were larger and thicker as compared to the controls. Scanning electron microscopy demonstrated an increased dermis thickness as compared to pre-treatment. All patients that answered to the follow up reported satisfaction during assessment. The satisfaction of the patients was very good and excellent in 45% of cases. The results of the needle-shaping procedure are natural with no scaring or down time. Moreover, the result is lasting even for 1 year, depending always on the subject's lifestyle and general health condition.

Colorectal cancer (CRC) is one of the four leading causes of cancer-related mortality worldwide. Even though over the past few decades the global scientific community has made tremendous efforts to understand this entity, many questions remain to be raised on this issue and even more to be answered. Epidemiological findings have unveiled numerous environmental and genetic risk factors, each one contributing to a certain degree to the final account of new CRC cases. Moreover, different trends have been revealed regarding the age of onset of CRC between the two sexes. That, in addition to newly introduced therapeutic approaches for various diseases based on androgens, anti-androgens and anabolic hormones has raised some concerns regarding their possible carcinogenic effects or their synergistic potential with other substances/risk factors, predisposing the individual to CRC. Notably, despite the intense research on experimental settings and population studies, the conclusions regarding the majority of anabolic substances are ambiguous. Some of these indicate the carcinogenic properties of testosterone, dihydrotestosterone (DHT), growth hormone and insulin-like growth factor (IGF) and others, demonstrating their neutral nature or even their protective one, as in the case of vitamin D. Thus, the synergistic nature of anabolic substances with other CRC risk factors (such as type 2 diabetes mellitus, metabolic syndrome and smoking) has emerged, suggesting a more holistic approach.

Stump appendicitis is defined as interval inflammation of any residual appendicular tissue, after an appendicectomy. We present a systematic review of case series and case reports on stump appendicitis, emphasising on risk factors, diagnosis and surgical management. The English literature (1945–2018) was reviewed, using PubMed, Embase and GoogleScholar, combining the terms “appendix”, “appendicitis”, “stump”, “residual”, “recurrent” and “retained”. In total, 127 studies were included, describing 164 patients (males 59%, mean age 36 ± 17 years). Index surgery was open in 59% and laparoscopic in 38%. It was described as “difficult” or “complicated” in 31%. 20% of patients reported episodes of recurrent abdominal pain during the time interval between index and stump appendicitis (range 2 weeks to 60 years, median 2 years). Right lower quadrant pain was the most frequent complain (88%), leukocytosis was found in 56%, whereas 92% of patients underwent imaging testing, which was diagnostic or highly suspicious in 67.5%. Mean delay between beginning of symptoms and surgery was 2.4 ± 2.3 days. The operative approach was open in 61% and laparoscopic in 35% of cases. The operation was characterised as “difficult” or “complicated” in 45%. In the majority (88%), a completion stump appendicectomy was performed, with 11% requiring more extensive procedures. Mean length of resected stump was 3.1 ± 1.6 cm (range 0.5–10 cm). Stump appendicitis may occur following both open and laparoscopic approach, when the residual stump is > 0.5 cm. Its clinical significance lies in the delayed diagnosis, leading to higher incidence of complications and the need for more extensive surgery.

The human organism coexists with its microbiota in a symbiotic relationship. These polymicrobial communities are involved in many crucial functions, such as immunity, protection against pathogens, and metabolism of dietary compounds, thus maintaining homeostasis. The oral cavity and the colon, although distant anatomic regions, are both highly colonized by distinct microbiotas. However, studies indicate that oral bacteria are able to disseminate into the colon. This is mostly evident in conditions such as periodontitis, where specific bacteria, namely Fusobacterium nucrelatum and Porphyromonas gingivalis project a pathogenic profile. In the colon these bacteria can alter the composition of the residual microbiota, in the context of complex biofilms, resulting in intestinal dysbiosis. This orally-driven disruption promotes aberrant immune and inflammatory responses, eventually leading to colorectal cancer (CRC) tumorigenesis. Understanding the exact mechanisms of these interactions will yield future opportunities regarding prevention and treatment of CRC.

Diagnosing primary breast tumors of the axillary tail of Spence may be extremely challenging, since several lesions may be located in the axillary fossa. In the presented case, a 54-year-old post-menopausal Caucasian female patient presented to our institution complaining about a lump in her left axilla. The preoperative imaging modalities could not clarify whether the tumor is part of the tail of Spence or metastasis of the axillary lymph nodes. The diagnosis of primary adenocarcinoma of the axillary tail of Spence was made during a quadrantectomy of the left breast after the clavipectoral fascia, which constitutes the sole anatomical boundary between breast and axilla, was identified.

Background This study aims to present the feasibility of the open approach of hemilevator excision (HLE) as a promising alternative of the laparoscopic and/or robotic ones for the treatment of low rectal cancer extending to the ipsilateral puborectalis muscle. Methods A 60-year-old male patient with a high-grade differentiated rectal adenocarcinoma at the right side of the lower rectum invading puborectalis muscle. The proposed operation consists of a combination of extralevator abdomino-perineal excision (ELAPE), intersphicteric resection (ISR), and low anterior resection (LAR) since it resects the ipsilateral to tumor levator ani muscle (LAM) from its attachment at the internal obturator fascia and the deep part of ipsilateral external anal sphincter (EAS), while the distal part of dissection is completed in the intersphincteric space taking out the internal anal sphincter (IAS). At the contralateral side of the tumor, the dissection plane follows the classic route of LAR. Results Pathology proved the oncologic adequacy of resection. MRI at the fourth postoperative week showed clearly the right aspect of anorectal junction free of tumor. Anorectal manometry revealed a fair anorectal function which is in accordance with the findings of clinical assessment of patient after restoring large bowel continuity (post-op Wexner score, 7). Conclusion This is the first case of the open HLE that seems to be a good alternative compared to ELAPE or conventional APR, as it offers oncologic adequacy and a fair anorectal function.

Pancreatic cancer (PC) and ovarian cancer (OC) consist two major causes of mortality associated with abdominal malignancies. Their common characteristic to manifest delayed clinical symptomatology results in ineffective therapeutic strategy at the time of diagnosis. Particularly for PC, overall survival percentages after curative surgery still remain disappointing despite the significant progress achieved in several aspects of disease management, including a better understanding of biological background/natural history; innovative diagnostic methods; and availability of new therapeutic modalities mainly focused on chemoradiotherapy and targeted therapy. On the other hand, patients with OC with early-stage disease (confined exclusively in ovaries) exhibit a quite high curative rate. These data necessitate the development and usage of more sophisticated tools such as biomarkers, aiming to improve diagnosis, prognosis, and prediction of patients with PC and OC. In this chapter, an overview on this challenging issue is presented.

Rectal anatomy is one of the most challenging concepts of visceral anatomy, even though currently there are more than 23,000 papers indexed in PubMed regarding this topic. Nonetheless, even though there is a plethora of information meant to assist clinicians to achieve a better practice, there is no universal understanding of its complexity. This in turn increases the morbidity rates due to iatrogenic causes, as mistakes that could be avoided are repeated. For this reason, this review attempts to gather current knowledge regarding the detailed anatomy of the rectum and to organize and present it in a manner that focuses on its clinical implications, not only for the colorectal surgeon, but most importantly for all colorectal cancer-related specialties.

Surgical site infections (SSIs) determine an increase in hospitalization time and antibiotic therapy costs. The aim of this study was to identify the germs involved in SSIs in patients from the Clinical Emergency County Hospital of Craiova (SCJUC) and to assess their resistance to antimicrobials, with comparisons between surgical wards and the intensive care unit (ICU). The biological samples were subjected to classical bacteriological diagnostics. Antibiotic resistance was tested by disc diffusion. We used hierarchical clustering as a method to group the isolates based upon the antibiotic resistance profile. The most prevalent bacterial species isolated were Staphylococcus aureus (S. aureus; 50.72%), followed by Escherichia coli (E. coli; 17.22%) and Pseudomonas aeruginosa; 10.05%). In addition, at lower percentages, we isolated glucose-non-fermenting, Gram-negative bacteria and other Enterobacteriaceae. The antibiotic resistance varied greatly between species; the most resistant were the non-fermenting Gram-negative rods. E. coli exhibited lower resistance to third generation cephalosporins, quinolones and carbapenems. By contrast, Klebsiella was resistant to many cephalosporins and penicillins, and to a certain extent to carbapenems due to carbapenemase production. The non-fermenting bacteria were highly resistant to antibiotics, but were generally sensitive to colistin. S. aureus was resistant to ceftriaxone (100%), penicillin (91.36%), amoxicillin/clavulanate (87.50%), amikacin (80.00%) and was sensitive to levofloxacin, doxycycline, gentamycin, tigecycline and teicoplanin. The Enterobacteriaceae resistance was only slightly higher in the ICU, particularly to carbapenems (imipenem, 31.20% in the ICU vs. 14.30% in the surgical wards; risk ratio = 2.182). As regards Staphylococcus species, but for non-fermenting bacteria, even if the median was almost the same, the antibiotic resistance index values were confined to the upper limit in the ICU. The data gathered from this study may help infection control teams to establish effective guidelines for antibiotic therapies in various surgical procedures, in order to minimize the risk of developing SSIs by the efficient application of the anti-infection armamentarium.

In this data article, the potential role of p53 tumor suppressor gene (p53) on the attachment ability of MCF-7 breast cancer cells was investigated. In our main article, “IGF-I/ EGF and E2 signaling crosstalk through IGF-IR conduit point affect breast cancer cell adhesion” (K. Voudouri, D. Nikitovic, A. Berdiaki, D. Kletsas, N.K. Karamanos, G.N. Tzanakakis, 2016) [1], we describe the key role of IGF-IR in breast cancer cell adhesion onto fibronectin (FN). p53 tumor suppressor gene is a principal regulator of cancer cell proliferation. Various data have demonstrated an association between p53 and IGF-IR actions on cell growth through its’ putative regulation of IGF-IR expression. According to our performed experiments, p53 does not modify IGF-IR expression and does not affect basal MCF-7 cells adhesion onto FN. Moreover, technical details about the performance of adhesion assay onto the FN substrate were provided.

Osteosarcoma (OS) is a primary bone tumor of mesenchymal origin mostly affecting children and adolescents. The OS extracellular matrix (ECM) is extensively altered as compared to physiological bone tissue. Indeed, the main characteristic of the most common osteoblastic subtype of OS is non‑mineralized osteoid production. Parathyroid hormone (PTH) is a polypeptide hormone secreted by the chief cells of the parathyroid glands. The PTH-related peptide (PTHrP) may be comprised of 139, 141 or 173 amino acids and exhibits considerate N‑terminal amino acid sequence homology with PTH. The function of PTH/PTHrP is executed through the activation of the PTH receptor 1 (PTHR1) and respective downstream intracellular pathways which regulate skeletal development, bone turnover and mineral ion homeostasis. Both PTHR1 and its PTH/PTHrP ligands have been shown to be expressed in OS and to affect the functions of these tumor cells. This review aims to highlight the less well known aspects of PTH/PTHrP functions in the progression of OS by focusing on ECM-dependent signaling.

Cypermethrin (CY) is a frequently used class II pyrethroid pesticide, while piperonyl butoxide (PBO) plays a major role in the pesticide formulation of synthetic pyrethroids. Synthetic pyrethroids are metabolized in mammals via oxidation and ester hydrolysis. PBO can prevent the metabolism of CY and enhances its pesticide effect. While this potentiation effect reduces the amount of pesticide required to eliminate insects, it is not clear how this mixture affects mammals. In our in vivo experiment, New Zealand white male rabbits were exposed to low and high doses of CY, PBO, and their combinations, for 4 months. Genotoxicity and cytotoxicity were monitored by measuring binucleated cells with micronuclei (BNMN), micronuclei (MN) and the cytokinesis block proliferation index (CBPI) in lymphocytes. After two months of exposure, a statistically significant increase in the frequency of BNMN was observed for all exposed animals (p

The aimof this study is to clarify the effect of cypermethrin (CY) on the oxidative stress (OS) and inflammation status of animals exposed to it and the synergistic role of piperonyl butoxide (PB0).Markers of oxidative stress, such as total antioxidant activity (TAC), protein carbonyls, hemoglobin (Hb), reduced glutathione (GSH), thiobarbituric-acid reactive substances (TBARS), along with the telomerase activity in PBMCs (peripheral blood mononuclear cells) were analyzed.Oxidative stress markers showed statistically significant differences between groups in TAC (p b 0.001), GSH (p = 0.018) and CAT activity (p = 0.029), which depended on dose and combined effect of both compounds. Telomerase activity also showed a statistically significant difference between all groups (F = 43.48, df=6, 14, p b 0.001)with cypermethrin, piperonyl butoxide and the co-exposed groups being significantly different fromthe control group (p b 0.05). Significance: The observed results for TBARS, GSH, Hb, TAC, Crbnls and CAT from our exposed groups showed altered levels compared to control groups that could be linked to doses and combined effects of each chemical substance (cypermethrin and piperonyl butoxide). Oxidative stress markers suggest that cypermethrin, piperonyl butoxide and the co-exposed groups, induce oxidative stress as well as induction of telomerase activity.