Surgical oncology during the post-COVID-19 era: What is next?

During first outburst of COVID-19, several strategies had been applied for surgical oncology patients to minimize COVID-19 transmission. COVID-19 infection seemed to compromise survival and major complication rates of surgical oncology patients. However, survival, tumor progression and recurrence rates of surgical oncology patients were associated to the consequences of COVID-19 pandemic on their management. In addition, the severity of COVID-19 infections has been downgraded. Therefore, management of surgical oncology patients should be reconsidered.

Antiproliferative and cytotoxic action of N-(p-coumaroyl) serotonin in lung cancer cells.

PURPOSE: Lung cancer is among the leading causes of cancer-related cases and cancer-associated deaths. Tumor cells frequently acquire chemoresistance and, due to that, new therapies are always needed in the fight against cancer. Pharmaceutical plants continue to offer novel compounds as anticancer therapies. METHODS: We studied the action of N-p-coumaroyl-serotonin (CS), a natural compound from Centaurea seed and safflower on a lung adenocarcinoma cell line. Cytotoxic or antiproliferative effect was studied using the MTT assay. Cell cycle, caspase-8 activation, mitochondrial membrane potential (MMP) and expression of CD15/CD56/CD24/CD44/CD58/CD71 were studied by flow cytometry. RESULTS: CS exterted antiproliferative and cytotoxic activity, independent of mitochondrial membrane disruption. This compound caused S phase arrest and a decrease in the expression of CD24/CD44/CD58/CD71. CONCLUSION: This is the first report on the in vitro action of CS against lung cancer, necessitating further studies towards its use as a potential anticancer agent.

N-(p-coumaroyl) serotonin induces cell cycle arrest and apoptosis in breast cancer cells.

PURPOSE: Breast cancer is the most commonly diagnosed malignancy among women. Breast cancer cells may develop resistance to current chemotherapy, thus new chemotherapeutic agents are urgently needed. METHODS: A major number of drugs with anticancer activity have been isolated from plants. Herewith, we investigated for the first time the effect of N-(p-coumaroyl) serotonin (CS), isolated from Centaurea seed on a drug-resistant breast carcinoma (MCF-7) cells. Viability and proliferation of the cells were examined with trypan blue exclusion assay and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Caspace-8, cell cycle, and CD24/CD44/CD56/ CD58/CD71/CD15 expression were tested with flow cytometry. RESULTS: Treatment with CS significantly reduced cell viability. Induction of cell death and cell cycle arrest was confirmed with flow cytometry. After treatment with CS, there was a dose-dependent decrease in CD24/CD44/CD58/CD71 expression, whereas there was no change in CD56 and CD15 expression. CONCLUSION: The treatment of breast cancer cells with CS may represent a novel therapeutic strategy and requires further investigation.

Giant Metastatic Liver Tumor of Unknown Primary Origin: Thoracic Autopsy Solves the Mystery.

A 59-year-old male patient was hospitalized in the Internal Medicine Department for investigation of hepatic metastases from an unknown primary neoplasm. During the hospitalization the patient died from acute myocardial infarction. The autopsy revealed a 8.2 kilograms (kg) liver that was diffusely infiltrated by whitish metastatic masses. No other tumor was detected, apart from a 2.5 centimeters (cm) pulmonary nodule next to the right intermediate bronchus that was histologically compatible with small cell lung cancer (SCLC). Despite the fact that hepatic metastases from SCLCs are common, diffuse metastatic hepatomegaly from a malignant pulmonary nodule are rarely seen. Given that the most common cause of malignancy-related death is lung cancer, early diagnosis and appropriate management of pulmonary nodules is of paramount importance.

How can we effectively address the paraneoplastic dermatomyositis: Diagnosis, risk factors and treatment options.

PURPOSE: Dermatomyositis (DM) represents an auto-immune inflammatory myopathy. In this review, we analyzed the incidence of DM as a clinical manifestation highlighting the peculiar clinical and treatment characteristics of this disease when occurring in the context of different malignancies. METHODS: A systematic literature review was performed based on database search in PubMed/Medline and included English articles until December 2016. RESULTS: In up to 20% of cases DM appears as a paraneoplastic syndrome associated with multiple malignancies such as ovarian, breast, prostate, lung, nasopharyngeal and colorectal cancer, and non-Hodgkin lymphomas. It can be presented either before, in the time, or after cancer diagnosis. Systemic sclerosis and mixed connective-tissue disease represent common coinciding disorders. Particular caution should be given in the radiotherapy because the microvascular endothelial radiation damage and autoimmune inflammatory collagen vascular disease caused by DM may be additive. There is a higher risk of late toxicity in the presence of other concurrent vascular diseases, including diabetes, hypertension or administration of chemotherapy. Prednisone represents the first-line treatment option but immunosuppressive drugs such as azathioprine and methotrexate may also be incorporated in the therapeutic armamentarium especially when DM is associated with malignancy. Intravenous immunoglobulin could be a promising alternative in prednisone-resistant cases. The effectiveness of therapies with antigen-specific agents such as monoclonal antibodies is currently under investigation. CONCLUSIONS: Timely diagnosis coupled with a treatment plan focused on muscular endurance and improvement of skin lesions and other symptoms offer a favorable response to therapy along with the achievement of a higher quality of life for these patients.

Addressing the post-irradiation hypothalamic-pituitary endocrine abnormalities of brain tumors in pediatric patients.

PURPOSE: Hypothalamic-pituitary axis is susceptible to radiotherapy, causing endocrine disorders to childhood cancer survivors. We conducted a systematic review in order to assess the radiation-induced toxicity that leads to hormone secretion abnormalities and their severity in children with brain tumors. METHODS: The data were collected by relevant studies on PubMed and EMBASE. Articles up to December 2016 were included. We selected studies which focused on children patients (<18 yr old) with brain tumors treated with radiotherapy and the consequences for their endocrine system. RESULTS: Growth hormone (GH) deficiency was the most common post-irradiation abnormality among children cancer survivors, followed by gonadotrophin (GT), thyroid stimulating hormone (TSH), corticotropin (ACTH) and prolactin (PRL) disorders. CONCLUSIONS: The age of the patient, total radiotherapy dose, number of fractions, fraction size and the duration of treatment seem to determine the severity of these disturbances.

EndoVenous-assisted invaginated stripping of the great saphenous vein: A pilot and feasibility study.

Objective: By incorporating an endovascular component into Great Saphenous Vein stripping, EndoVenous-assisted Invaginated Stripping (EVIS) aims to make the procedure minimally invasive. A study was conducted to investigate the surgical intervention. Methods: Sketches and videos were used to illustrate the technical aspects of EVIS. A prospective cohort study included 20 patients with chronic venous insufficiency (CVI). Results: EVIS is performed as a day-surgery. Technical success was 100%, and no complications were recorded. The mean operative time was 45 minutes, intraoperative pain score was 4.8, post-operative pain was 2.5, 1.8, 1.2, 0.5 at 48 hours, 1, 4, and 12 weeks, respectively. The mean blood loss was 15 mL, and the mean length of the GSV strapped was 19 cm. The follow-up duplex showed a reduction in the diameter of the residual GSV stump. Conclusions: EVIS is a combination of standard techniques that may prove valuable in managing CVI.

Translation and cross-cultural adaptation of the Kidney Transplant Questionnaire 25 to Greek.

BACKGROUND: Kidney transplantation leads to continuous improvement in the survival rates of kidney transplant recipients (KTRs) and has been established as the treatment of choice for patients with end-stage kidney disease. Health-related quality of life (HRQoL) has become an important outcome measure. It is highly important to develop reliable methods to evaluate HRQoL with disease-specific questionnaires. AIM: To translate the disease-specific instrument Kidney Transplant Questionnaire 25 (KTQ-25) to the Greek language and perform a cross-cultural adaptation. METHODS: The translation and adaptation of the original English version of the KTQ-25 to the Greek language were performed based on the International Quality of Life Assessment. RESULTS: Eighty-four KTRs (59 males; mean age 53.5 ± 10.7 years; mean estimated glomerular filtration rate 47.7 ± 15.1 mL/min/1.73 m2; mean transplant vintage 100.5 ± 83.2 months) completed the Greek version of the KTQ-25 and the 36-item Short-Form Health Survey, and the results were used to evaluate the reliability of the Greek KTQ-25. The Cronbach alpha coefficients for all the KTQ-25 dimensions were satisfactory (physical symptoms = 0.639, fatigue = 0.856, uncertainty/fear = 0.661, appearance = 0.593, emotions = 0.718, total score = 0.708). The statistically significant correlation coefficients among the KTQ-25 dimensions ranged from 0.226 to 0.644. The correlation coefficients of the KTQ-25 dimensions with the SF-36 physical component summary (PCS) ranged from 0.196 to 0.550; the correlation coefficients of the KTQ-25 with the SF-36 mental component summary (MCS) ranged from 0.260 to 0.655; and the correlation coefficients of the KTQ-25 with the total scores with the SF-36 PCS and MCS were 0.455 and 0.613, respectively. CONCLUSION: According to the findings, the Greek version of the KTQ-25 is valid and reliable for administration among kidney transplant patients in Greece.

Complete mesogastric excision for gastric cancer: is it the future of gastric cancer surgery?

Gastric cancer remains undoubtedly one of the most common and deadly cancers worldwide. The global incidence shows wide geographic variation with a high prevalence in Asia. Besides that, there are evident differences in epidemiology, histopathology, tumor location, diagnosis and treatment strategy between east and west countries. Gastric cancer represents an aggressive disease, with many factors influencing its development and also recurrence after surgical resection. New knowledge of disease spread and new routes of metastases are now emerging and the 'novel' concept of complete mesogastric excision for gastric cancer is under consideration and debate. This article aims to analyze and highlight this new concept after a careful literature review, offering also a view toward the future.

Differences in the Profile of Circulating Immune Cell Subsets in Males with Type 2 Cardiorenal Syndrome versus CKD Patients without Established Cardiovascular Disease.

Maladaptive activation of the immune system plays a key role in the pathogenesis of chronic kidney disease (CKD). Our aim was to investigate differences in circulating immune cells between type 2 cardiorenal syndrome (CRS-2) patients and CKD patients without cardiovascular disease (CVD). CRS-2 patients were prospectively followed up, with the primary endpoint being all-cause and cardiovascular mortality. METHOD: A total of 39 stable males with CRS-2 and 24 male CKD patients matched for eGFR (CKD-EPI) were enrolled. A selected panel of immune cell subsets was measured by flow cytometry. RESULTS: Compared to CKD patients, CRS-2 patients displayed higher levels of proinflammatory CD14++CD16+ monocytes (p = 0.04) and T regulatory cells (Tregs) (p = 0.03), lower lymphocytes (p = 0.04), and lower natural killer cells (p = 0.001). Decreased lymphocytes, T-lymphocytes, CD4+ T-cells, CD8+ T-cells, Tregs, and increased CD14++CD16+ monocytes were associated with mortality at a median follow-up of 30 months (p < 0.05 for all). In a multivariate model including all six immune cell subsets, only CD4+ T-lymphocytes remained independent predictors of mortality (OR 0.66; 95% CI 0.50-0.87; p = 0.004). CONCLUSION: Patients with CRS-2 exhibit alterations in immune cell profile compared to CKD patients of similar kidney function but without CVD. In the CRS-2 cohort, CD4+ T-lymphocytes independently predicted fatal cardiovascular events.

Neutrophil Extracellular Traps and Pancreatic Cancer Development: A Vicious Cycle.

Neutrophil extracellular traps (NETs) are a neutrophil-generated extracellular network of chromatin and chromatin-bound molecules with antimicrobial potency. Recent data suggest that NETs are associated with cancer progression and cancer-associated hypercoagulability. Pancreatic adenocarcinoma (PDAC) is a lethal type of cancer in which hypercoagulability and cancer-related thrombosis are among the main complications. In the current report, we summarize the available data on the interplay between NET formation and PDAC development. We conclude that NETs support a dual role during PDAC progression and metastasis. Their formation is on the one hand an important event that shapes the cancer microenvironment to support cancer cell proliferation, invasion and metastasis. On the other hand, NETs may lead to cancer-associated thrombosis. Both mechanisms seem to be dependent on distinct molecular mechanisms that link inflammation to cancer progression. Collectively, NET formation may contribute to the pathogenesis of PDAC, while during cancer development, the proinflammatory environment enables the induction of new NETs and thrombi, forming a vicious cycle. We suggest that targeting NET formation may be an effective mechanism to inhibit both PDAC development and the accompanying hypercoagulability.

Colour Duplex and/or Contrast-Enhanced Ultrasound Compared with Computed Tomography Angiography for Endoleak Detection after Endovascular Abdominal Aortic Aneurysm Repair: A Systematic Review and Meta-Analysis.

This study aims to assess the role of Color Duplex Ultrasound with or without contrast media for surveillance following endovascular aortic aneurysm repair (EVAR). A systematic search of the literature published until April 2022 was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The pooled rates of endoleak detection through Contrast-Enhanced or Color Duplex Ultrasound (CEUS or CDUS) and Computed Tomography Angiography (CTA) with 95% confidence intervals (CIs) were estimated using random-effect analysis. Thirty-eight studies were considered eligible for inclusion. The total number of patients in the included studies was 5214 between 1997 and 2021. The overall pooled rate of endoleak detection using CDUS and CTA was 82.59% and 97.22%, while the rates for CEUS and CTA were 96.67% and 92.82%, respectively. The findings of the present study support the use of the CEUS for endoleak detection. However, it should be integrated into institutional protocols for EVAR surveillance to further evaluate its clinical utility in the post-EVAR period before it can be recommended as the sole imaging modality after EVAR.

Intraoperative Flow Cytometry for the Characterization of Gynecological Malignancies.

Cell-cycle analysis has shown the presence of aneuploidy to be associated with poor prognosis. We developed an innovative rapid cell-cycle analysis protocol (the Ioannina protocol) that permitted the intraoperative identification of neoplastic cells in a plethora of malignancies. Herein, we aimed to investigate the potential role of cell-cycle analysis in the intraoperative characterization of gynecological malignancies. Women who underwent surgery for gynecological malignancies in our institution over a three-year period were included in this study. Permanent section pathology evaluation was used as the gold standard for malignancy evaluation. Total accordance was observed between flow cytometry and pathology evaluation. In total, 21 aneuploid cancers were detected following DNA index calculation. Of these, 20 were hyperploid and 1 was hypoploid. In addition, tumor samples were characterized by a significantly lower percentage of cells in G0/G1, as well as an induced tumor index. The response time for flow cytometry to obtain results was 5-6 min per sample. It seems that flow cytometry analyses for intraoperative tumor evaluation can be safely expanded to gynecological malignancies. This is a novel practical approach that has been proven valuable in several tumor types to date, and also seems to be reliable for gynecological malignancies. Intraoperative flow cytometry is expected to be crucial in decisions of lymph node dissection in endometrial cancers, due to its rapid response regarding the tumor invasion of part or all of the myometrial thickness. In this way, the surgeon can quickly modify the plane of dissection. Our results warrant the further investigation of applying iFC in larger, multicenter studies.

Secretory Phospholipase A2 Digital Expression Analysis in Colon Adenocarcinoma.

BACKGROUND/AIM: Phospholipases A2 represent a family of enzymes that regulate the metabolism of phospholipids by hydrolyzing them into fatty acids. Secretory phospholipase A2 (SPLA2) catalyzes the calcium-dependent 2-acyl groups hydrolysis to produce 3-sn-phosphoglycerides. This study aimed to investigate SPLA2 expression in colon adenocarcinoma (CA). MATERIALS AND METHODS: Thirty (n=30) formalin-fixed, paraffin-embedded primary CA tissue sections were used and analyzed. Immunohistochemistry was performed using an anti-SPLA2 antibody. Digital image analysis was also implemented for evaluating objectively the corresponding protein expression levels. RESULTS: Increased SPLA2 protein expression (high & moderate immunostaining levels) was observed in 23/30 (76.6%) cases, whereas 7/30 (23.4%) CA tissues demonstrated low protein levels. High expression levels were detected in 9/30 (30%) cases. SPLA2 overall expression was strongly associated with tumor diameter (p=0.004), whereas other statistically significant associations were not observed (stage: p=0.971, inflammatory infiltration: p=0.795; carcinoma location: p=0.340; differentiation grade: p=0.748; sex: p=0.369; ulceration: p=0.433). CONCLUSION: SPLA2 over-expression is observed in significant subsets of CAs correlating with advanced tumor growth progression (increased diameter). SPLA2 seems to influence endogenous cell responses by its crucial enzymatic activity and can potentially be a biomarker for monitoring CA patients.

Proof-of-Concept Pilot Study on Comprehensive Spatiotemporal Intra-Patient Heterogeneity for Colorectal Cancer With Liver Metastasis.

Introduction: The mechanisms underlying high drug resistance and relapse rates after multi-modal treatment in patients with colorectal cancer (CRC) and liver metastasis (LM) remain poorly understood. Objective: We evaluate the potential translational implications of intra-patient heterogeneity (IPH) comprising primary and matched metastatic intratumor heterogeneity (ITH) coupled with circulating tumor DNA (ctDNA) variability. Methods: A total of 122 multi-regional tumor and perioperative liquid biopsies from 18 patients were analyzed via targeted next-generation sequencing (NGS). Results: The proportion of patients with ITH were 53% and 56% in primary CRC and LM respectively, while 35% of patients harbored de novo mutations in LM indicating spatiotemporal tumor evolution and the necessity of multiregional analysis. Among the 56% of patients with alterations in liquid biopsies, de novo mutations in cfDNA were identified in 25% of patients, which were undetectable in both CRC and LM. All 17 patients with driver alterations harbored mutations targetable by molecularly targeted drugs, either approved or currently under evaluation. Conclusion: Our proof-of-concept prospective study provides initial evidence on potential clinical superiority of IPH and warrants the conduction of precision oncology trials to evaluate the clinical utility of I PH-driven matched therapy.

Impact of peroxiredoxin-6 expression on colon adenocarcinoma.

PURPOSE: Peroxiredoxins (Prdxs) represent a family of proteins that act as antioxidant enzymes and are involved in a variety of metabolic functions including mainly the intracellular hydrogen peroxide (H2O2) levels reduction. Especially, Prdx-6 protein encoded by the PRDX6 gene (1q25.1) regulates also phospholipid modifications and induces response to oxidative stress and injuries. Our aim was to investigate the expression of Prdx-6 in colon adenocarcinoma (CA). METHODS: A series of 30 formalin-fixed, paraffin-embedded primary CAs tissue sections were used and analyzed. Immunohistochemistry was performed using an anti-Prdx-6 antibody. Digital image analysis was also implemented for evaluating objectively the protein expression levels on the corresponding stained cells. RESULTS: Prdx-6 protein overexpression (increased immunostaining levels) was observed in 12/30 (40%) cases, whereas 18/30 (60%) CA tissues demonstrated low to moderate protein levels, respectively. Prdx-6 overall expression was strongly associated with the stage of the examined tumors (p=0.011), whereas other statistical significances were not assessed (inflammatory infiltration: p=0.364; carcinoma location: p=0.93; differentiation grade: p=0.517; tumor diameter: p=0.983; ulceration: p=0.622). CONCLUSIONS: Prdx-6 overexpression is observed in a significant subset of CAs correlating with aggressive biological behavior (advanced stage). Prdx-6 is a crucial enzyme for oxidative stress/injury endogenous cell response and should be an interesting agent as a biomarker and potential therapeutic target.

Posterior Scleritis as a Paraneoplastic Syndrome in Colon Cancer: A Case Report

This study presents a rare case of unilateral posterior scleritis as an ophthalmic manifestation of a paraneoplastic syndrome. A 61-year-old man presented to our department complaining of gradual worsening of vision in his left eye. Visual acuity was 10/10 and 3/10 in his right and left eye, respectively. He also mentioned that he experienced posterior ocular pain while sleeping at night, but was otherwise asymptomatic. His past ophthalmic and medical history were clear. A thorough clinical, imaging (fundus photography, optical coherence tomography, fluorescein angiography, and B-scan), and laboratory investigation was carried out. A diagnosis of posterior scleritis was made, but no obvious cause or underlying disease was identified even after a thorough systematic assessment. Regular follow-up within the next few months did not reveal any further pathological findings. Finally, 6 months after the initial presentation, the patient was diagnosed with colon cancer. Posterior scleritis can present as an ophthalmic manifestation of a paraneoplastic syndrome in patients with an underlying malignancy, even months before the presentation of systemic symptoms and diagnosis of the underlying disease. In conclusion, in patients (especially older adults) with posterior scleritis, the possibility of a malignant neoplasia must not be ignored or underestimated (paraneoplastic syndrome).