Publications by authors named "John Tsiaoussis"

54 Publications

The Anatomy in Greek Iatrosophia during the Ottoman domination era.

J BUON 2021 Jan-Feb;26(1):33-38

Laboratory of Anatomy, Medical School, University of Crete, 70013 Heraklion, Greece.

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.
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March 2021

Revisiting Amyand's Hernia: A 20-Year Systematic Review.

World J Surg 2021 Feb 17. Epub 2021 Feb 17.

Creta Interclinic Hospital, Heraklion, Crete, Greece.

Purpose: 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.

Methods: 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.

Results: 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.

Conclusion: 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.
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http://dx.doi.org/10.1007/s00268-021-05983-yDOI Listing
February 2021

A systematic review of splenic artery variants based on cadaveric studies.

Surg Radiol Anat 2021 Jan 22. Epub 2021 Jan 22.

Department of Anatomy and Surgical Anatomy, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloníki, Greece.

Purpose: 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.

Methods: The current study presents a systematic review of the English literature on the SA variations, with emphasis on its terminal branching patterns.

Results: 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%.

Conclusion: Knowledge of the SA aberrations is important for surgeons and radiologists involved in angiographic interventions.
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http://dx.doi.org/10.1007/s00276-020-02675-5DOI Listing
January 2021

Immunotherapy in Solid Tumors and Gut Microbiota: The Correlation-A Special Reference to Colorectal Cancer.

Cancers (Basel) 2020 Dec 25;13(1). Epub 2020 Dec 25.

Laboratory of Translational Oncology, School of Medicine, University of Crete, 70013 Heraklion, Greece.

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.
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http://dx.doi.org/10.3390/cancers13010043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7795476PMC
December 2020

Evaluation of the Role of Circulating Tumor Cells and Microsatellite Instability Status in Predicting Outcome of Advanced CRC Patients.

J Pers Med 2020 Nov 18;10(4). Epub 2020 Nov 18.

Laboratory of Translational Oncology, Medical School, University of Crete, 70013 Heraklion, Greece.

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 and CEACAM5/EpCAM CTC, respectively, and 9.1% of the patients had mRNA-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.
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http://dx.doi.org/10.3390/jpm10040235DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7712177PMC
November 2020

Intestinal Microbiota in Colorectal Cancer Surgery.

Cancers (Basel) 2020 Oct 16;12(10). Epub 2020 Oct 16.

Laboratory of Anatomy, School of Medicine, University of Crete, 70013 Heraklion, Greece.

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.
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http://dx.doi.org/10.3390/cancers12103011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7602998PMC
October 2020

Current and Future Trends in Molecular Biomarkers for Diagnostic, Prognostic, and Predictive Purposes in Non-Melanoma Skin Cancer.

J Clin Med 2020 Sep 4;9(9). Epub 2020 Sep 4.

Laboratory of Anatomy-Histology-Embryology, Medical School, University of Crete, 71110 Heraklion, Crete, Greece.

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.
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http://dx.doi.org/10.3390/jcm9092868DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7564050PMC
September 2020

PKM2 Expression as Biomarker for Resistance to Oxaliplatin-Based Chemotherapy in Colorectal Cancer.

Cancers (Basel) 2020 Jul 25;12(8). Epub 2020 Jul 25.

Laboratory of Translational Oncology, School of Medicine, University of Crete, 71003 Heraklion, Greece.

The purpose of the current study is to investigate the prognostic significance of M2 isoform of pyruvate kinase (PKM2) expression loss in patients with operable colon cancer (CC). Two hundred sixty-two specimens from patients with stage-III or high-risk stage-II CC (group-A) treated with adjuvant fluoropyrimidine and oxaliplatin chemotherapy (FOLFOX), 118 specimens from metastatic CC patients (group-B) treated with FOLFOX, and 104 metastatic CC patients (group-C) treated with irinotecan-based chemotherapy were analyzed for , and mRNA expression, as well as exon2 and mutations. High mRNA expression was correlated with left-sided located primaries ( = 0.001, group-A; = 0.003, group-B; = 0.001, group-C), high-grade tumors ( = 0.001, group-A; = 0.017, group-B; = 0.021, group-C), microsatellite-stable tumors ( < 0.001, group-A), pericolic lymph nodes involvement ( = 0.018, group-A), and mRNA expression ( = 0.002, group-A; = 0.008, group-B; = 0.006, group-C). High mRNA expression was correlated with significantly lower disease free survival (DFS) ( = 0.002) and overall survival (OS) ( = 0.001) in the group-A. Similarly, mRNA expression was associated with significantly decreased progression free survival (PFS) ( = 0.001) and OS ( = 0.001) in group-B. On the contrary, no significant association for the mRNA expression has been observed with either PFS ( = 0.612) or OS ( = 0.517) in group-C. To conclude, the current study provides evidence for the prediction of mRNA expression oxaliplatin-based treatment resistance.
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http://dx.doi.org/10.3390/cancers12082058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7465271PMC
July 2020

The Role of Vitamin D Receptor Gene Polymorphisms in Colorectal Cancer Risk.

Cancers (Basel) 2020 May 27;12(6). Epub 2020 May 27.

Laboratory of Translational Oncology, Medical School, University of Crete, 70013 Heraklion, Greece.

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; I (I), rs7975232; sub. I (I), rs2228570; I (I) and rs1544410, s I (I) polymorphisms of the VDR gene to colorectal carcinogenesis (CRC) and progression. Peripheral blood was obtained from 397 patients with early operable stage II/III ( = 202) and stage IV ( = 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 ( < 0.001). All of the mutant genotypes detected were also significantly associated with stage IV ( < 0.001), leading to significantly decreased survival ( < 0.001). Moreover, all four polymorphisms were significantly associated with (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) ( = 0.001, < 0.001 and = 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.
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http://dx.doi.org/10.3390/cancers12061379DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352496PMC
May 2020

The Prognostic Value of the Detection of Microbial Translocation in the Blood of Colorectal Cancer Patients.

Cancers (Basel) 2020 Apr 24;12(4). Epub 2020 Apr 24.

Laboratory of Translational Oncology, Medical School, University of Crete, 70013 Heraklion, Crete, Greece.

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 -galactosidase gene of , glutamine synthase gene of and .8S rRNA of Significantly higher rates of all microbial fragments, but , detected were observed in the CRC patients ( < 0.001); such detection of all four microbial fragments was also significantly associated with the metastatic disease ( < 0.001), leading to shorter survival rates ( < 0.001). Tumor location in the right colon also significantly correlated with shorter survival ( = 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' survival.
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http://dx.doi.org/10.3390/cancers12041058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226464PMC
April 2020

Large intestine embryogenesis: Molecular pathways and related disorders (Review).

Int J Mol Med 2020 Jul 21;46(1):27-57. Epub 2020 Apr 21.

Laboratory of Anatomy‑Histology‑Embryology, Medical School, University of Crete, 71110 Heraklion, Greece.

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.
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http://dx.doi.org/10.3892/ijmm.2020.4583DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7255481PMC
July 2020

A novel approach regarding the anti-aging of facial skin through collagen reorganization.

Exp Ther Med 2020 Jan 27;19(1):717-721. Epub 2019 Nov 27.

Laboratory of Clinical Virology, Medical School, University of Crete, 71003 Heraklion, Greece.

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.
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http://dx.doi.org/10.3892/etm.2019.8254DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6913239PMC
January 2020

Role of anabolic agents in colorectal carcinogenesis: Myths and realities (Review).

Oncol Rep 2019 Dec 3;42(6):2228-2244. Epub 2019 Oct 3.

Laboratory of Anatomy‑Histology‑Embryology, Medical School, University of Crete, 71110 Heraklion, Greece.

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.
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http://dx.doi.org/10.3892/or.2019.7351DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6826302PMC
December 2019

Detailed and applied anatomy for improved rectal cancer treatment.

Ann Gastroenterol 2019 Sep-Oct;32(5):431-440. Epub 2019 Jul 22.

Laboratory of Anatomy-Histology-Embryology, Medical School of Heraklion, University of Crete (Taxiarchis Konstantinos Nikolouzakis, John Tsiaoussis).

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.
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http://dx.doi.org/10.20524/aog.2019.0407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6686088PMC
July 2019

Oral Bacteria and Intestinal Dysbiosis in Colorectal Cancer.

Int J Mol Sci 2019 Aug 25;20(17). Epub 2019 Aug 25.

Laboratory of Anatomy-Histology-Embryology, Medical School, University of Crete, 71110 Heraklion, Greece.

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 and 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.
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http://dx.doi.org/10.3390/ijms20174146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6747549PMC
August 2019

Unfinished Business: A Systematic Review of Stump Appendicitis.

World J Surg 2019 11;43(11):2756-2761

Creta Interclinic Hospital, Heraklion, Crete, Greece.

Background: 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.

Methods: 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).

Results: 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).

Conclusions: 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.
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http://dx.doi.org/10.1007/s00268-019-05101-zDOI Listing
November 2019

An anatomic anal sphincter-saving procedure for rectal cancers located at anorectal junction.

World J Surg Oncol 2019 Aug 2;17(1):131. Epub 2019 Aug 2.

Laboratory of Anatomy-Histology-Embryology, Medical School of Heraklion, University of Crete, Heraklion, Greece.

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.
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http://dx.doi.org/10.1186/s12957-019-1672-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6676583PMC
August 2019

Non-Recurrent Right Laryngeal Nerve: a Rare Anatomic Variation Encountered During a Total Thyroidectomy.

Acta Medica (Hradec Kralove) 2019 ;62(2):69-71

University Department of Surgery, General and Oncologic Hospital of Kifissia "Agii Anargiri", Athens, Greece.

The non-recurrent laryngeal nerve (nRLN) is a rare anatomic variation that every head and neck surgeon must be aware of, in order to avoid intraoperative injury which leads to postoperative morbidity. We are reporting a case of a nRLN in a 47 year old female patient with medullary thyroid carcinoma who was surgically treated with total thyroidectomy and lymph node dissection. Both two inferior laryngeal nerves were identified, fully exposed and preserved along their cervical courses. However, we found that the right inferior laryngeal nerve was non-recurrent and directly arised from the cervical vagal trunk, entered the larynx after a short transverse course and parallel to the inferior thyroid artery. The safety of thyroid operations is dependent on high index of suspicion, meticulous identification and dissection of laryngeal nerves either recurrent or non-recurrent. This leads to minimum risk of iatrogenic damage of the nerves. Complete knowledge of the anatomy of these neural structures, including all their anatomic variations is of paramount importance.
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http://dx.doi.org/10.14712/18059694.2019.105DOI Listing
February 2020

The clavipectoral fascia as the unique anatomical criteria for distinguishing breast parenchymal lesions from axillary lymph node metastasis.

J Surg Case Rep 2019 May 9;2019(5):rjz135. Epub 2019 May 9.

General and Oncologic Hospital of Kifissia 'Agioi Anargyroi', Athens, Greece.

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.
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http://dx.doi.org/10.1093/jscr/rjz135DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6507663PMC
May 2019

An anatomic aberration and a surgical challenge: Mediastinal parathyroid adenoma anterior the pericardium. A case report.

Int J Surg Case Rep 2019 6;58:153-156. Epub 2019 Apr 6.

Anatomy and Histology Laboratory, School of Nursing, University of Athens, Greece; University Department of Surgery, General and Oncologic Hospital of Kifissia "Agii Anargiri'', Athens, Greece.

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.
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http://dx.doi.org/10.1016/j.ijscr.2019.04.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6495084PMC
April 2019

Anatomical variation of the trajectory of the brachiocephalic artery encountered during parathyroid adenoma excision. A rare case report and a surgical challenge.

Int J Surg Case Rep 2019 6;58:138-141. Epub 2019 Apr 6.

Anatomy and Histology Laboratory, School of Nursing, University of Athens, Greece; University Department of Surgery, General and Oncologic Hospital of Kifissia "Agii Anargiri'', Athens, Greece.

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.
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http://dx.doi.org/10.1016/j.ijscr.2019.04.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6529586PMC
April 2019

Effects of single and combined toxic exposures on the gut microbiome: Current knowledge and future directions.

Toxicol Lett 2019 Sep 27;312:72-97. Epub 2019 Apr 27.

Laboratory of Toxicology, Medical School, University of Crete, Voutes, 71409 Heraklion, Crete, Greece; Department of Analytical, Toxicology, Pharmaceutical Chemistry and Pharmacognosy, Sechenov University, 119991 Moscow, Russia. Electronic address:

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.
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http://dx.doi.org/10.1016/j.toxlet.2019.04.014DOI Listing
September 2019

WITHDRAWN: An anatomic aberration and a surgical challenge: Mediastinal parathyroid adenoma anterior the pericardium. A case report.

Int J Surg Case Rep 2019 21;57:106-109. Epub 2019 Mar 21.

Anatomy and Histology Laboratory, School of Nursing, University of Athens, Greece; University Department of Surgery, General and Oncologic Hospital of Kifissia "Agii Anargiri", Athens, Greece.

The Publisher regrets that this article is an accidental duplication of an article that has already been published in “International Journal of Surgery Case Reports, 57C (2019) 106–109”, https://doi.org/10.1016/j.ijscr.2019.03.014. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal
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http://dx.doi.org/10.1016/j.ijscr.2019.03.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6444067PMC
March 2019

Superior mesenteric artery syndrome: a rare case of upper gastrointestinal obstruction.

J Surg Case Rep 2019 Mar 12;2019(3):rjz054. Epub 2019 Mar 12.

University Department of Surgery, General and Oncologic Hospital of Kifissia 'Agii Anargiri', Athens, Greece.

Superior mesenteric artery (SMA) or Wilkie's syndrome is a rare clinical entity of partial or complete duodenal obstruction. The pathogenic mechanism is an acute angulation of the SMA which leads to compression of the third part of the duodenum between the SMA and the aorta. This is commonly due to loss of fatty tissue as a result of a variety of debilitating conditions. Its treatment is initially conservative and in case of failure, surgical therapy is unavoidable. We present a case of a 68-year-old female patient who presented in our Department with of dehydration after persistent vomiting for months. After complete radiologic workup, SMA syndrome was diagnosed and was successfully treated operatively. SMA syndrome might be a diagnostic challenge and must be always included in the differential diagnosis of upper gastrointestinal obstruction. Consequently, this paper aims to increase the awareness of a rare entity of duodenal obstruction.
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http://dx.doi.org/10.1093/jscr/rjz054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6413377PMC
March 2019

Effect of systemic treatment on the micronuclei frequency in the peripheral blood of patients with metastatic colorectal cancer.

Oncol Lett 2019 Mar 7;17(3):2703-2712. Epub 2019 Jan 7.

Laboratory of Anatomy-Histology-Embryology, Medical School, University of Crete, 71110 Heraklion, Greece.

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.
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http://dx.doi.org/10.3892/ol.2019.9895DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6365930PMC
March 2019

Intestinal microbiota and colorectal cancer: a new aspect of research.

J BUON 2018 Sep-Oct;23(5):1216-1234

Laboratory of Anatomy-Histology-Embryology, Medical School, University of Crete, 71110 Heraklion, Greece.

Colon holds a complex microbial community, which is crucial for maintaining homeostasis and regulating metabolic functions, supporting the intestinal barrier and controlling immune responses. Previous studies have supported a link between intestinal microbiota and colorectal cancer (CRC). Based on these fndings, the present review analyzed the numerous interactions that occur between microbiota and CRC, starting from the role of intestinal microbiota in colonic homoeostasis. Intestinal microbiota is a cause of CRC and involves various mechanisms such as chronic inflammation, the production of genotoxins causing DNA impairment and/or the biosynthesis of toxic compounds. Moreover, basic metabolic factors such as short-chain fatty acids (SCFAs) and bile acids are included in CRC pathogenesis. Different pathogenic pathways have been reported among different CRC regions (proximal or distal). Variations in the microbial populations are reported between the CRC from these colonic sites, possibly reflecting the bacterial dysbiosis and bioflm distribution. Bowel preparation is essential prior to colonoscopy and surgery; there is, however, minor consensus on the effects of this procedure on intestinal microbiota, notably with regard to the long-term outcomes. With regard to the therapeutic strategy in CRC, the intestinal microbiota is further involved in the modulation of the host response to chemotherapeutic agents (5-fluorouracil and irinotecan) by the interference with drug efcacy and by adverse effects and associated toxicity. In addition, the newly emerged research on CRC immunotherapy reveals an important interplay between intestinal microbiota and the immune system, which includes the possibility of targeting microbiota for the enhancement of anticancer treatment. Additional studies will further clarify the interaction between microbiota and CRC, resulting in the development of alternative therapeutic strategies by manipulating microbiota composition.
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August 2019

Middle colic vein draining to splenic vein: a rare anatomic variation encountered during a right hemicolectomy.

J Surg Case Rep 2018 Aug 15;2018(8):rjy220. Epub 2018 Aug 15.

University Department of Surgery, General and Oncologic Hospital of Kifissia 'Agii Anargiri', Athens, Greece.

Right or subtotal colectomy either open or laparoscopic may be a challenging operation owing to technical difficulties. One of these, is to identify a safe and adequate dissection plane, ligating and dissecting lymph nodes around middle colic vessels. The purpose of this study was to depict a rare anatomic variation of middle colic vein (MCV) draining to splenic vein. We report the case of a 55-year-old male patient, who was subjected to a right hemicolectomy for an adenocarcinoma in the ascending colon. During dissecting the transverse mesocolon from the greater omentum, for complete mesocolic excision (CME), we encountered that the MCV drained in the splenic vein. With respect of this rare anatomic variability, CME was completed without hemorrhage. Our aim is to depict that deep knowledge of MCV anatomy and its variations is of paramount importance to achieve CME and to avoid dangerous or massive bleeding.
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http://dx.doi.org/10.1093/jscr/rjy220DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6101511PMC
August 2018

The metabolism of imidacloprid by aldehyde oxidase contributes to its clastogenic effect in New Zealand rabbits.

Mutat Res Genet Toxicol Environ Mutagen 2018 May - Jun;829-830:26-32. Epub 2018 Mar 19.

Laboratory of Toxicology, Medical School, University of Crete, Voutes, 71409 Heraklion, Crete, Greece. Electronic address:

Imidacloprid (IMI) is a systemic, chloro-nicotinyl insecticide classified in Regulation N° 1272/2008 of the European Commision as "harmful if swallowed and very toxic to aquatic life, with long-lasting effects". IMI is metabolized in vitro both by aldehyde oxidase (AOX) (reduction) and by cytochrome P450s enzymes (CYPs). In the present study, the AOX inhibitor sodium tungstate dihydrate (ST) was used to elucidate the relative contribution of CYP 450 and AOX metabolic pathways on IMI metabolism, in male rabbits exposed to IMI for two months. To evaluate the inhibition effectiveness, various metabolite concentrations in the IMI and IMI + ST exposed groups were monitored. DNA damage was also evaluated in micronucleus (MN) and single cell electrophoresis (SCGC) assays in both groups, along with oxidative stress (OS) with the inflammatory status of the exposed animals, in order to clarify which metabolic pathway is more detrimental in this experimental setting. A significant increase in the frequency of binucleated cells with MN (BNMN, 105%) and micronuclei (MN, 142%) was observed after exposure to IMI (p < 0.001). The increase in the ST co-exposed animals was less pronounced (BNMN 75%, MN 95%). The Cytokinesis Block Proliferation Index (CBPI) showed no significant difference between controls and exposed animals at any time of exposure (p > 0.05), which indicates no cytotoxic effect. Similarly, comet results show that the IMI group exhibited the highest achieved tail intensity, which reached 70.7% over the control groups, whereas in the IMI + ST groups the increase remained at 48.5%. No differences were observed between all groups for oxidative-stress biomarkers. The results indicate that the AOX metabolic pathway plays a more important role in the systemic toxicity of IMI.
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http://dx.doi.org/10.1016/j.mrgentox.2018.03.002DOI Listing
June 2019