Highlighting the contribution of the Greek physician Theodoros Aretaios to the history of thyroidectomy.

Theodoros Aretaios (1829-1893), having pursued advanced studies at home and abroad and possessing a wide range of competences and interests, was among the first Greek physicians to produce educational treatises for both students and doctors of medicine. Among these is his medical treatise Surgery which deals with thyroid operations and goiter symptoms as well as post-operative lesions which included a record of his extensive experience, learned recommendations, deep insights, and advanced techniques. In this medical archive, which is preserved in the National Library of Greece, there is, for example, the physician's vivid description of a thyroidectomy that he performed which illustrates his expertise as a surgeon as well as the surgical knowledge of his times. Aretaios was not the first to perform this operation in Greece: he was, however, the first to document it, which he did for the benefit of his fellow Greeks and of surgeons worldwide.

Combination treatment of inflammatory bowel disease: Present status and future perspectives.

The treatment of patients with inflammatory bowel disease (IBD), especially those with severe or refractory disease, represents an important challenge for the clinical gastroenterologist. It seems to be no exaggeration to say that in these patients, not only the scientific background of the gastroenterologist is tested, but also the abundance of "gifts" that he should possess (insight, intuition, determination, ability to take initiative, etc.) for the successful outcome of the treatment. In daily clinical practice, depending on the severity of the attack, IBD is treated with one or a combination of two or more pharmaceutical agents. These combinations include not only the first-line drugs (e.g., mesalazine, corticosteroids, antibiotics, etc) but also second- and third-line drugs (immunosuppressants and biologic agents). It is a fact that despite the significant therapeutic advances there is still a significant percentage of patients who do not satisfactorily respond to the treatment applied. Therefore, a part of these patients are going to surgery. In recent years, several small-size clinical studies, reviews, and case reports have been published combining not only biological agents with other drugs (e.g., immunosuppressants or corticosteroids) but also the combination of two biological agents simultaneously, especially in severe cases. In our opinion, it is at least a strange (and largely unexplained) fact that we often use combinations of drugs in a given patient although studies comparing the simultaneous administration of two or more drugs with monotherapy are very few. As mentioned above, there is a timid tendency in the literature to combine two biological agents in severe cases unresponsive to the applied treatment or patients with severe extraintestinal manifestations. The appropriate dosage, the duration of the administration, the suitable timing for checking the clinical and laboratory outcome, as well as the treatment side-effects, should be the subject of intense clinical research shortly. In this editorial, we attempt to summarize the existing data regarding the already applied combination therapies and to humbly formulate thoughts and suggestions for the future application of the combination treatment of biological agents in a well-defined category of patients. We suggest that the application of biomarkers and artificial intelligence could help in establishing new forms of treatment using the available modern drugs in patients with IBD resistant to treatment.

PD-L1 Gene Polymorphisms rs822336 G>C and rs822337 T>A: Promising Prognostic Markers in Triple Negative Breast Cancer Patients

Background and Objectives: Triple-negative breast cancer (TNBC) is a highly heterogeneous subtype that is associated with unresponsiveness to therapy and hence with high mortality rates. In this study we aimed to investigate the prognostic role of the rs822336 G>C and rs822337 T>A polymorphisms of the PD-L1 (Programmed Death-Ligand 1) in TNBC patients. Materials and methods: Formalin-fixed paraffin-embedded tissues from 114 TNBC patients and blood samples from 124 healthy donors were genotyped, and subsequently extensive statistical analysis was performed in order to investigate the clinical value of these polymorphism in TNBC. Results: Regarding rs822336 G>C, we found that the CG genotype was the most common among women that harbored Stage IV breast tumors (81.8%; p = 0.022), recurred (38.9%; p = 0.02) and died (66.7%; p = 0.04). Similarly, the rs822337 T>A genotype AA is associated with worse prognosis, since it was the most common genotype among stage IV tumors (72.7%; p = 0.04) and in TNBC patients that relapsed (75%; p = 0.021) and died (81.5%; p = 0.004). Our statistical analysis revealed that the rs822336 G>C genotype CG and the rs822337 T>A allele AA are strongly associated with inferior DFS and OS intervals. Moreover, it was revealed that women harboring mutated genotypes of both SNPs had shorter disease-free (Kaplan−Meier; p = 0.037, Cox analysis; p = 0.04) and overall (Kaplan−Meier; p = 0.025, Cox analysis; p = 0.03) survival compared to patients having normal genotype of at least one SNP. Multivariate analysis also showed that the presence of mutated genotypes of both SNPs is a strong and independent marker for predicting shorter DFS (p = 0.02) and OS (p = 0.008). Conclusion: Our study revealed that PD-L1 rs822336 G>C and rs822337 T>A polymorphisms were differentially expressed in our cohort of TNBC patients, and that this distribution was associated with markers of unfavorable prognosis and worse survival.

Angiogenesis in gastrointestinal stromal tumors: From bench to bedside.

Gastrointestinal stromal tumors (GISTs) are rare neoplasms with an estimated incidence from 0.78 to 1-1.5 patients per 100000. They most commonly occur in the elderly during the eighth decade of life affecting predominantly the stomach, but also the small intestine, the omentum, mesentery and rectosigmoid. The available treatments for GIST are associated with a significant rate of recurrent disease and adverse events. Thorough understanding of GIST's pathophysiology and translation of this knowledge into novel regimens or drug repurposing is essential to counter this challenge. The present review summarizes the existing evidence about the role of angiogenesis in GIST's development and progression and discusses its clinical underpinnings.

Implant infections after breast reconstruction surgery following mastectomy: Experience from a Greek breast unit.

BACKGROUND: Despite the dominance of implant-based breast reconstruction after mastectomy, during recent years, it has been correlated to some complications. The aim of this study is to present the Greek experience about management of implant infections after breast reconstructions and to investigate the relationship between possible risk factors and breast pocket fluid cultures. METHODS: In total, 260 patients underwent implant-based breast reconstruction due to breast cancer in our center from 2016 until 2020. 46 patients, that underwent implant or expander replacement after breast reconstruction due to mastectomy were included in the present study. RESULTS: 260 patients underwent breast reconstruction in our center and in 46 (18%) of them an implant replacement was required. 21 patients (8%) presented clinically with an implant infection, but 12 of them (5%) had positive cultures from the breast pocket fluid. On the contrary, 25 patients (10%) presented no clinical signs of implant infection, but 5 of them (2%) had a positive culture. In addition, we demonstrated a correlation between implant infection and positive cultures (p = 0.009), along with an association between chemotherapy before implant placements and negative cultures (p = 0.035). Finally, the most common pathogen was Staphylococcus epidermidis (29%), followed by Escherichia coli (24%) and Staphylococcus aureus (18%). CONCLUSION: Implant infection still remains a very serious complication after breast reconstruction surgery. The establishment of a therapeutic protocol, with specific antimicrobial and surgical targets seems as an effective strategy against implant infections.

Severe anaphylactic reaction after blue dye injection for sentinel lymph node biopsy in breast surgery: Report of two cases and literature review.

Anaphylactic reactions, and especially the severe ones (types III and IV), should be kept in mind as considerable adverse effects while using blue dyes for SLNB.

Place of hyperthermic intraperitoneal chemotherapy in the armament against pancreatic adenocarcinoma: A survival, mortality and morbidity systematic review.

Pancreatic adenocarcinoma is one of the deadliest types of cancer worldwide, with a 5-year survival rate of 8% despite recent treatment advancements. The present systematic review aimed to investigate the role of hyperthermic intraperitoneal chemotherapy (HIPEC) following surgical resection for pancreatic adenocarcinoma, with or without peritoneal carcinomatosis. A systematic search of the MEDLINE and SCOPUS electronic databases was performed according to PRISMA guidelines. All possible relevant articles published between January 1980 and May 2019 were retrieved using multiple search terms associated with HIPEC and pancreatic adenocarcinoma. The initial search resulted in 1,244 reports, which condensed to 41 reports following screening of titles and abstracts, and subsequently to four reports following full-text thorough examination. The four reports included involved a prospective cohort study of HIPEC use in resectable pancreatic adenocarcinoma, and three retrospective studies of HIPEC use following cytoreductive surgery for peritoneal carcinomatosis due to pancreatic adenocarcinoma, resulting in a total of 47 patients. The overall survival ranged between 2 and 62 months, and the hospital mortality rate was 8.5%. Morbidity (34%) was mainly attributed to anastomotic leak or respiratory failure. Due to the small sample size and low quality of evidence of the included studies, no valid conclusions could be drawn. Therefore, further studies are required to justify the use of HIPEC as an adjuvant therapy in resectable pancreatic adenocarcinoma, while cytoreductive surgery and HIPEC in peritoneal carcinomatosis of pancreatic origin seems not only not useful but also unsafe at this level of evidence.

Anxiety and Depression Affect Early Postoperative Pain Dimensions after Bariatric Surgery.

Uncontrolled postoperative pain and prolonged immobilization after bariatric surgery have been associated with increased postoperative complications and prolonged hospitalization. The aim of our study was to evaluate the postoperative pain that follows bariatric surgery and identify any psychological factors that may affect the early postoperative perception of pain. The study included 100 patients with obesity (women, n = 61; age 37.4 ± 9.9 years, mean ± standard deviation; Body Mass Index (BMI) 47.6 ± 6.5 kg/m2) who underwent bariatric surgery. Preoperative anxiety and depression were evaluated by the Hospital Anxiety and Depression Scale (HADS), and the quantitative and qualitative dimension of early postoperative pain were evaluated by the McGill Pain Questionnaire Short Form (MPQ-SF). Furthermore, the postoperative analgesia protocol was recorded for each patient. Pain declined gradually during the first 24 h postoperative. Although preoperative anxiety had no correlation with the overall pain of postoperative Day 0, patients with a higher level of preoperative anxiety had significantly more intense and more unpleasant pain at 1 h post operation. In addition, depression influences both the intensity and unpleasantness of pain at different time points (1 h, 4 h and 24 h postoperative). Preoperative pain correlated with educational level, but not with age, BMI, gender, marital status, smoking and surgery type. In conclusion, preoperative anxiety and depression influence the early postoperative pain after bariatric surgery, and their preoperative identification is of major importance to enhance the implementation of fast-track postoperative protocols to prevent complications and prolonged hospitalization.

The Effects of Ascorbic Acid and U-74389G on Renal Ischemia-Reperfusion Injury in a Rat Model.

BACKGROUND/AIM: U-74389G and ascorbic acid protect the cells from oxidation. This study aimed to depict their role in ischemia-reperfusion injury in a renal rat model. MATERIALS AND METHODS: Sixty Wistars rats were randomized into six groups of 10 animals each. Group A Ischemia 30 min, reperfusion 60 min; Group B Ischemia 30 min, reperfusion 120 min; Group C Ischemia 30 min, ascorbic acid administration, reperfusion 60 min; Group D Ischemia 30 min, ascorbic acid administration, reperfusion 120 min; Group E Ischemia 30 min, U-74389G administration, reperfusion 60 min; Group F Ischemia 30 min, U-74389G administration, reperfusion 120 min. We then collected tissue and blood samples. RESULTS: Histology and the significantly decreased malondialdehyde and tumor necrosis factor-α levels indicated that ascorbic acid was superior to U-74389G, at pre-defined time intervals. CONCLUSION: Ascorbic acid and U-74389G ameliorated renal damage induced by ischemia-reperfusion injury, suggesting a therapeutic effect.

Molecular Classification and Future Therapeutic Challenges of Triple-negative Breast Cancer.

Triple-negative breast cancer (TNBC) is an extremely diverse group of breast tumors, with aggressive clinical behavior, higher rates of distant recurrence and worse overall survival compared to other types of breast cancers. The genetic, transcriptional histological and clinical heterogeneity of this disease has been an obstacle in the progression of targeted therapeutic approaches, as a ubiquitous TNBC marker has not yet been discerned. In terms of that, current studies focus on the classification of TNBC tumors in subgroups with similar characteristics in order to develop a treatment specialized for each group of patients. To date, a series of gene expression profiles analysis in order to identify the different molecular subtypes have been used. Complementary DNA microarrays, PAM50 assays, DNA and RNA sequencing as well as immunohistochemical analysis are some of the methods utilized to classify TNBC tumors. In 2012, the Cancer Genome Atlas (TCGA) Research Network conducted a major analysis of breast cancers using six different platforms, the genomic DNA copy number arrays, DNA methylation, exome sequencing, messenger RNA arrays, microRNA sequencing and reverse-phase protein arrays, in order to assort the tumors in homogenous subgroups. Since then, an increasing number of breast cancer data sets are being examined in an attempt to distinguish the classification with biological interpretation and clinical implementation. In this review, the progress in molecular subtyping of TNBC is discussed, providing a brief insight in novel TNBC biomarkers and therapeutic strategies.

Kounis syndrome after patent blue dye injection for sentinel lymph node biopsy.

BACKGROUND: Kounis syndrome (KS) has been described as an acute coronary syndrome (ACS) associated with an anaphylactic reaction. Several triggers have been identified and the diagnostic and treatment process can be challenging. CASE: A 58-year-old, female patient diagnosed with breast cancer and no history of allergies had subcutaneous injection of patent blue V dye for sentinel lymph node biopsy (SLNB). Intraoperatively, she developed anaphylactic shock and was transferred to the intensive care unit (ICU). A few hours later, electrocardiographic alterations and elevation of blood troponin were observed. Emergency coronary angiography revealed no occlusive lesions in coronary vessels. Further investigation in the allergy department set the diagnosis of KS. CONCLUSION: There are just ten cases of perioperative KS in the literature so far and here we present the first one triggered by patent blue V dye for sentinel node biopsy.

Mega-megacolon: a case report.

PURPOSE: Large bowel obstruction and megacolon formation secondary to complicated diverticulitis is rare. METHODS: We present a case of an 84-year-old woman surviving large bowel obstruction and mega-megacolon formation secondary to complicated diverticulitis, with an impressive presentation of abdominal distention. RESULTS: The patient's symptoms, laboratory test results, and imaging were consistent with large bowel obstruction. The patient underwent urgent exploratory laparotomy. Upon entry in the abdomen, it was unexpected that the extreme colonic wall thickening had prevented perforation, indicating the longtime course of illness. The biopsy of the specimen from the site of the obstruction demonstrated an inflammatory obstructing mass. CONCLUSION: This report aims to point out the atypical and in-extremes presentation of an otherwise common disease.

Giant phyllodes tumor occupying the whole breast in a young female: feasibility of mastectomy and immediate reconstruction.

Giant phyllodes tumors are rare fibroepithelial breast neoplasms typically >10 cm by definition. The best investigation for preoperative diagnosis is core biopsy, although it is often difficult for the pathologist to distinguish fibroadenomas from phyllodes tumors and determine the level of malignant potential. The wide excision is the appropriate therapy for phyllodes tumors taking into consideration that mastectomy may be required for huge phyllodes tumors. In the modern era of breast tissue expanders and breast implants, immediate breast reconstruction is feasible. We present a case report of a patient with a giant phyllodes tumor of 24 cm diameter who underwent mastectomy and immediate breast reconstruction with breast tissue expander.

Predictive factors for breast lesion excision system (BLES) accuracy and safety in stereotactic biopsy of suspicious calcifications.

AIM: To retrospectively assess the effectiveness and safety of BLES stereotactic biopsy of suspicious calcifications and investigate possible predictive factors for underestimation. METHODS AND MATERIALS: Between January 2014 and January 2016, 400 biopsies of suspicious calcifications were performed in our Department using the BLES stereotactic device. The mean age of our population was 58.5 years (range 39-78 years). The final surgical results were used as gold standard. The effectiveness of the method was statistically evaluated. Mammographic size, grade, molecular type, and presence of comedo type/necrosis were assessed as predictive factors. RESULTS: 90/400 (22.5%) cases were cancers (20% invasive cancers, 80% non-invasive cancers). 38/400 cases were atypical lesions (9.5%). No underestimation was found in atypical lesions that underwent surgery (29/38 cases). Downgrade was achieved in 45.5% of cases (with complete removal in 34.4%), concordance in 43.3%, and upgrade was found in 15.5% of the cases; the initial mammographic size and the grade of the cancers were found to be statistically significant predictive factors. The total complication rate was 8.75%. CONCLUSIONS: Breast lesion excision system is a highly accurate and safe stereotactic biopsy technique of suspicious calcifications with low underestimations and high downgrade/removal rates with the potential to alter the final surgical decision in selected cases.

Performance of breast lesion excision system (BLES) in complete removal of papillomas presented mammographically as groups of calcifications.

OBJECTIVES: To retrospectively assess the stereotactic one-pass BLES performance in excision of small groups of calcifications seen on mammogram that proved to be papillomas. METHODS: Between January 2014 and January 2016, 37/400 cases (9.2%) of stereotactic BLES biopsies performed in our department due to suspicious calcifications proved to be papillomas. Lesions with atypia underwent surgical removal and lesions with no atypia were followed up for 2 years. BLES and surgical histology results, radiological removal and 2-years stability were statistically analysed to assess BLES performance in biopsy and excision of papillomas. RESULTS: The mean mammographic size of papillomas was 6.54 mm (st dev = 3.85, range 2 mm-17 mm) and within the size excised by the BLES needle (20 mm). 4/37 cases (10.8%) showed atypia. BLES excision was achieved in 29/37 cases (78.4%); radiological removal based on post BLES mammogram was achieved in 25/29 cases (86.2%). In the remaining 8/37 cases the papillomas were seen at the ink of the specimens' margins; 3/8 cases showed residual calcifications on post-BLES mammogram. The BLES histology result of removal and the mammographic size of the papillomas were found to be statistically significant predictive factors of excision (p < 0,001, Fisher's exact test, Mann Whitney test). Follow up mammograms showed no change for a period of 2 years. CONCLUSION: BLES is a safe and accurate technique to biopsy papillomas with high success rates of excision which could potentially minimize the need of subsequent radiological or surgical excision.

Role of one-pass breast lesion excision system in complete excision of high-risk breast lesions with atypia expressed as clusters of microcalcifications.

PURPOSE: To assess the role of the breast lesion excision system (BLES) in complete removal of clusters of microcalcifications found on mammogram proved histologically to be high-risk lesions with cell atypia. METHODS AND MATERIALS: Three hundred ninety-four consecutive women (mean age 58.5 years, range 39-78 years) with 400 clusters of suspicious microcalcifications underwent stereotactic biopsy using the intact BLES device between January 2014 and January 2016. All cases proved histologically to be high-risk lesions were subsequently assessed for complete removal. The underestimation rate was also assessed. RESULTS: Thirty-eight out of 400 (9.5%) lesions were high-risk lesions with atypia with mean size 7.63 mm (st. dev. = 4.03 mm) which was within the size that the BLES needle can excise (20 mm). Four (10.5%) papillomas with atypia, 14 (36.8%) cases with flat epithelial atypia (FEA), 10 (26.3%) cases with lobular intraepithelial neoplasia (LIN-LIN 1, LIN 2), 8 (21.2%) with atypical ductal hyperplasia (ADH) and 2 (5.3%) cases with mucocele-like lesions (MLL) with atypia were found. Twenty-nine out of 38 lesions had subsequent surgery. Complete excision was achieved in 23/29 lesions (79.3%). No underestimation was found. Two-year mammographic stability was found in all lesions. Non-parametric statistical analysis showed no other significant predictive factor for complete excision apart from the distance of the lesions from the specimen margins (p = 0.031 Mann-Whitney test). CONCLUSION: One-pass BLES intact biopsy technique is a safe method of complete removal of high-risk atypical lesions with high accuracy rates for certain histologies and could be potentially used as an alternative excision method to diagnostic surgery in selected cases. KEY POINTS: • Breast lesion excision system (BLES) is an image-guided biopsy technique that uses radiofrequency to remove an intact piece of tissue including the target breast neoplasm. • Breast lesion excision system (BLES) under stereotactic guidance is able to accurately biopsy high-risk breast lesions expressed mammographically as clusters of suspicious microcalcifications. • BLES under stereotactic guidance is an accurate technique for en bloc excision of selected cases of small clusters of suspicious microcalcifications proved to be high-risk lesions with histopathologically disease-free margins of excision.