Protocol design for randomized clinical trial to compare underwater cold snare polypectomy to conventional cold snare polypectomy for non-pedunculated colon polyps of size 5-10 mm (COLDWATER study).

BACKGROUND: Colorectal cancer is internationally the third leading cause of death from a malignant disease. The aim of screening colonoscopy in adults > 45 years of age is early diagnosis and treatment of precancerous polyps. Endoscopic polyp removal (polypectomy) can be achieved with various techniques depending on the size, morphology, and location of the polyp. According to current guidelines, small non-pedunculated polyps should be removed with a cold snare after the colorectal lumen has been insufflated with air (conventional cold snare polypectomy).In recent years, several studies have described the benefits of water aided colonoscopy, as well as the safety and efficacy of underwater cold snare polypectomy for large colon polyps. However, there are insufficient data on conventional and underwater techniques for small polyps, the most commonly diagnosed colorectal polyps. METHODS: We have designed a prospective randomized double-blind clinical trial to compare the safety and efficacy of conventional and underwater cold snare polypectomy for non-pedunculated polyps 5-10 mm in size. A total of 398 polyps will be randomized. Randomization will be carried out using the random numbers method of Microsoft Excel 2016. The primary endpoint is the muscularis mucosa resection rate. Secondary endpoints are the depth and percentage of R0 excisions, complications, and the recurrence rate at follow-up endoscopy 6-12 months after polypectomy. DISCUSSION: We hypothesize underwater polypectomy will result in a higher muscularis mucosa resection rate. The results of our study will provide useful data for the development of guidelines in polypectomy techniques for non-pedunculated polyps 5-10 mm in size. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov, NCT05273697.

Laparoscopic appendectomy vs open appendectomy during pregnancy: a systematic re-view.

BACKGROUND: Acute appendicitis and cholecystitis during pregnancy are the most common non-obstetrical surgical emergencies and can create severe clinical issues. Surgical treatment tends to be the method physicians recommend due to its tolerability and safety. During pregnancy, surgical intervention should minimize fetal risk without compromising the mother's health, although a favorable outcome for pregnant women is heavily dependent on accurate, early diagnosis and prompt intervention. Furthermore, the physicians should remain informed on the differences in current techniques to optimize the outcome of the operation. METHODS: This article performs a systematic review of the literature to examine whether laparoscopic treatment of acute appendicitis in pregnancy is a better option when compared to open surgery. We searched all major medical databases, identified the most relevant published studies on the subject, and performed a statistical analysis to answer that question. RESULTS: We identified 15 studies for inclusion, and their data were extracted. The resulting pool referred to 2,837 pregnant patients. Of those included patients, 1,103 underwent laparoscopic surgery and 1,656 had open surgery. All surgeries occurred in the second trimester. For laparoscopic surgery, the fetal demises rate was 2.44 % (27 deaths), and the preterm deliveries rate was 9.79 % (108 deliveries) as opposed to open surgery with a fetal demise rate of 2.64 % (48 deaths), and preterm deliveries rate at 10.7 % (178 deliveries). CONCLUSIONS: Our meta-analysis and data suggest that laparoscopic appendectomy is a safer option for treatment. There is a reduced risk of fetal demise and preterm delivery for pregnant women. HIPPOKRATIA 2022, 26 (1):1-6.

The effect of per os colchicine administration in combination with fenofibrate and N-acetylcysteine on triglyceride levels and the development of atherosclerotic lesions in cholesterol-fed rabbits.

OBJECTIVE: Atherosclerosis is a chronic inflammatory disease promoted by pro-inflammatory cytokines produced by NOD-, LRR- and pyrin domain-containing protein 3 (NLRP 3) inflammasome. Colchicine is an anti-inflammatory agent that inhibits inflammasome's action and stabilizes atherosclerotic lesions. N-acetylcysteine (NAC) reduces low-density lipoprotein (LDL) oxidation, metalloproteinase levels, and foam cell count and volume. Fenofibrate also has antioxidant, anti-inflammatory, and anticoagulant properties while also having a beneficial effect on the vasomotor function of the endothelium. The purpose of this study is to investigate the effect of per os colchicine administration in combination with fenofibrate and NAC on triglyceride levels and the development of atherosclerotic lesions in cholesterol-fed rabbits. MATERIALS AND METHODS: Twenty-eight male, 2 months old New Zealand White rabbits were separated into four groups and were fed with different types of diet for 7 weeks: standard, cholesterol 1% w/w, cholesterol 1% w/w plus colchicine 2 mg/kg body weight plus 250 mg/kg body weight/day fenofibrate, and cholesterol 1% w/w plus colchicine 2 mg/kg body weight plus 15 mg/kg body weight/day NAC. Blood samples were drawn from all animals. Lipid profiles were assessed, and interleukin 6 (IL-6) measurements were performed using an enzyme-linked immunosorbent assay (ELISA) kit. Histologic examination was performed on aorta specimens stained with eosin and hematoxylin. Aortic intimal thickness was evaluated using image analysis. RESULTS: Colchicine administration in combination with fenofibrate or NAC statistically significantly reduced the extent of atherosclerotic lesions in aortic preparations. Co-administration of colchicine with NAC has a stronger anti-atherogenic effect than the colchicine plus fenofibrate regimen. Triglerycide levels were decreased in the colchicine plus fenofibrate group and the colchicine plus NAC group at the end of the experiment (p < 0.05), whereas the Cholesterol group had increased levels. A favorable significant lower concentration of IL-6 was detected in the colchicine plus NAC group vs. the other groups. CONCLUSIONS: In an experimental rabbit model, it appears that colchicine statistically significantly reduces the development of atherosclerosis of the aorta, especially in combination with NAC. Colchicine, as an NLRP3 inflammasome inhibitor, and NAC, as an agent that directly targets IL-6 signaling, can reduce the inflammatory risk. Fenofibrate enhances the attenuating role of colchicine on triglyceride levels. Clinical studies should investigate whether similar effects can be observed in humans.

Robotic-assisted parathyroidectomy and short-term outcomes: a systematic review of the literature.

Minimal invasive techniques in endocrine surgery were lately adopted by surgical teams due to significant complications related to inadequate operative space and high risk of injuring crucial surrounding structures, such as vessels and nerves. Over the last years, technological improvements introduced robotic systems and approaches in endocrine surgery. Several case reports and series have described the safety and efficacy of these procedures such as robotic thyroidectomy and robotic parathyroidectomy. In the current review, we included 15 studies which described robotic-assisted parathyroidectomy for cervical parathyroid adenoma, in patients diagnosed with primary hyperparathyroidism or secondary hyperparathyroidism. No significant negative short-term outcomes were observed, in terms of postoperative complications, such as temporary or permanent injury of RLN, postoperative hypoparathyroidism and blood loss. The cosmetic result was, definitely, superior in comparison to conventional open parathyroidectomy. Despite the fact that RAP is an effective and curative method for patients with PHPT or secondary hyperparathyroidism, there are no available randomized clinical trials to establish this modern procedure as a gold-standard treatment strategy for these patients.

Targeting histone deacetylases in endometrial cancer: a paradigm-shifting therapeutic strategy?

OBJECTIVE: Endometrial cancer is increasingly prevalent in western societies and affects mainly postmenopausal women; notably incidence rates have been rising by 1.9% per year on average since 2005. Although the early-stage endometrial cancer can be effectively managed with surgery, more advanced stages of the disease require multimodality treatment with varying results. In recent years, endometrial cancer has been extensively studied at the molecular level in an attempt to develop effective therapies. Recently, a family of compounds that alter epigenetic expression, namely histone deacetylase inhibitors, have shown promise as possible therapeutic agents in endometrial cancer. The present review aims to discuss the therapeutic potential of these agents. MATERIALS AND METHODS: This literature review was performed using the MEDLINE database; the search terms histone, deacetylase, inhibitors, endometrial, targeted therapies for endometrial cancer were employed to identify relevant studies. We only reviewed English language publications and also considered studies that were not entirely focused on endometrial cancer. Ultimately, sixty-four articles published until January 2018 were incorporated into our review. RESULTS: Studies in cell cultures have demonstrated that histone deacetylase inhibitors exert their antineoplastic activity by promoting expression of p21WAF1 and p27KIP1, cyclin-dependent kinase inhibitors, that have important roles in cell cycle regulation; importantly, the transcription of specific genes (e.g., E-cadherin, PTEN) that are commonly silenced in endometrial cancer is also enhanced. In addition to these abstracts effects, novel compounds with histone deacetylase inhibitor activity (e.g., scriptaid, trichostatin, entinostat) have also demonstrated significant antineoplastic activity both in vitro and in vivo, by liming tumor growth, inducing apoptosis, inhibiting angiogenesis and potentiating the effects of chemotherapy. CONCLUSIONS: The applications of histone deacetylase inhibitors in endometrial cancer appear promising; nonetheless, additional trials are necessary to establish the therapeutic role, clinical utility, and safety of these promising compounds.

The potential effect of biological sealants on colorectal anastomosis healing in experimental research involving severe diabetes.

Colorectal anastomoses continuous to pose a significant challenge in current surgical practice. Anastomotic leakage remains one of the most frequent and dramatic complications of colorectal surgery, even in centres of high specialisation. Diabetes is a well-established independent factor which results in higher anastomotic leakage rates. Fibrin sealants have been applied in experimental and clinical studies for the prevention of anastomotic dehiscence. However, little is known regarding their impact on diabetic patients. Several fibrin sealants have been proposed as adjunct to standard surgical techniques to prevent leakage from colonic anastomoses following the reversal of temporary colostomies, approved for general haemostasis. This review summarises current advances in colorectal anastomoses and provides evidence that may strengthen the need for tissue sealants in colorectal anastomoses of diabetic patients. We searched Medline (1966-2016) and Scopus (2004-2016) for current evidence in the field. To date, there is no evidence to support the use of fibrin sealants as an adjunct in diabetic patients who undergo colorectal surgery. Experimental animal models with extreme diabetes could be of significant use in the present field and further research is needed prior to application of fibrin sealants in a clinical setting.

A study concerning morphometry of abdominal aorta branches and abdominal viscera: relations and correlation.

Research interest on abdominal aorta branches and abdominal viscera morphometry is renewed by technological evolution and development of new radiologic and clinical applications including stent grafts and chemoembolisation materials. Despite that, data on morphometry of abdominal aorta branches and abdominal viscera are lacking. To investigate this subject authors performed a morphometric study on 50 adult fresh and embalmed Caucasian cadavers and examined abdominal aorta branches', kidney and spleen morphometry. Our results on arteries' morphometry did not differ significantly from those of the literature; yet, we discovered significant differences between fresh and embalmed cadavers on viscera morphometry, spleen and kidneys. We also found previously unreported correlations between abdominal aorta branches' morphometric characteristics. Even more, we identified correlations between regional arteries and viscera morphometric characteristics, proposing a new factor determining viscera development. Finally, we performed an extensive literature review so to place our results in an anatomic, embryologic and, even more, a clinical context. We believe that our results add knowledge on abdominal aorta branches and viscera morphometry and are valuable for clinical, radiological and surgical applications including visceral arteries' aneurysms investigation and treatment, chemoembolisation procedures, stent grafts design and transplantation.

Worse histological grade of proximal colorectal tumors and its relation with stage.

PURPOSE: Accumulated data seem to support the concept that proximal and distal colorectal cancers (CRC) should be considered as different disease entities. We investigated a particular aspect of this assumption by examining variation of stage and grade distribution according to tumor site in a Greek patients' group. METHODS: A total of 200 cases having had undergone surgery for primary CRC was retrospectively analysed. Fifty-seven proximal tumors were compared to 143 distal lesions regarding tumor stage (TNM I-IV) and grade of differentiation (well, moderate and poor). Grade distribution by site was also examined within each particular stage and within additional stage categories (I-II, III-IV, I-III, II-IV, II-III). RESULTS: There was an almost significant trend of distal tumors for earlier stage (I) presentation (p=0.055), whereas proximal cancers were more frequently diagnosed with stages II-III (p=0.08). Poorly differentiated lesions displayed a strong predilection for proximal site (p=0.002), while tumors with moderate differentiation were preferentially found distally (p=0.001). Such segmental differences in grade distribution were also ascertained within most particular stages and all additional stage subsets (especially the last three). Moreover, both the proximal and the poorly differentiated lesions showed a parallel decrease in their incidence during the study period. CONCLUSION: The consistently recorded worse histological pattern of proximal tumors implies a different biological behavior of these lesions possibly due to distinct tumorigenic pathways involved in their development, whereas their tendency for late stage presentation demands further investigation before considered supportive to this concept.

Quality of life in burn patients in Greece.

The Burn Specific Health Scale - Brief (BSHS-B) is one of the most commonly used instruments for the evaluation of quality of life after burn injury. It can be self-administered, and it is useful in evaluating psychopathological symptoms in burn victims. The aim of this study was to translate and culturally adapt the BSHS-B into Greek, assessing its internal consistency and validity. The cultural adaptation included forward and backward translation, reconciliation, and a pilot study. The Greek version was administered to a sample of 40 adult burn victims admitted to our Burn Centre. Internal consistency was verified using Cronbach's alpha, and construct validity was evaluated through correlation with the Short Form of Health Survey Questionnaire (SF-36) using Spearman analysis. The Cronbach alpha coefficient of the questionnaire's total score was 0.954, demonstrating that the internal consistency of the Greek version was very high. The test-retest coefficient using kappa correlation was 0.830 (p < 0.001). Significant correlations were identified between BSHS-B subscales and the SF-36 subscales - Physical and Social Functioning, and Emotional Role. Despite the limited size of the sample, the Greek version of the BSHS-B shows good reliability and construct validity and can be used in clinical practice for further evaluations of burn patients' quality of life.

La Burn Specific Health Scale (BSHS) - Brief (Echelle sanitaire spécifique pour les brûlures ­ version brève) constitue un des instruments les plus communs utilisés pour l'évaluation de la qualité de la vie post-brûlure. L'échelle, qui peut être auto-administrée, est utile pour évaluer les symptômes psychopathologiques chez les victimes de brûlures. Le but de cette étude était de traduire et d'adapter la BSHS sur le plan culturel pour être utilisée dans la langue grècque, avec une évaluation de sa cohérence et validité interne. L'adaptation culturelle comprenait la traduction littérale avec rétrotraduction et version intermédiaire, et une étude pilote. La version grecque a été administrée à un échantillon de 40 grands brûlés adultes traités dans notre centre des brûlés. La cohérence interne a été vérifiée moyennant l'alpha de Cronbach et la validité du construit a été évaluée par corrélation avec la Forme Brève du Questionnaireure sur la Santé (SF-36) utilisant l'analyse de Spearman. Le coefficient alpha de Cronbach du score total du questionnaire était 0,954, ce qui démontre que la cohérence interne de la version grecque était très élevée. Le coefficient test-retest utilisant la corrélation de kappa était de 0,830 (p < 0,001). Des corrélations significatives ont été constatées entre les sous-échelles BSHS et les sous-échelles de la SF-36 - Fonctionnement Physique e Social, et Rôle Emotionnel. Malgré les dimensions limitées de l'échantillon, la version grecque de l'BSHS-B montre une bonne fiabilité et validité de construit et peut être utilisée dans la pratique clinique pour d'autres évaluations de la qualité de la vie des brûlés.

Intraoperative radiation therapy on pancreatic cancer patients: a review of the literature.

Pancreatic cancer is rarely curable, and the overall survival rate at 5 years is under 4%. This study aimed to assess the efficacy, effectiveness and safety of intraoperative radiation therapy (IORT) as treatment in pancreatic cancer, by means of a systematic review of the literature. We searched Pubmed from 1980 until 2010 by means of prospective randomized trials. The aim was to assess the potential impact of IORT on local control, quality of life and overall survival. The search was restricted to articles published in English. IORT offers the opportunity to administer high doses of irradiation to areas of neoplastic involvement while attempting simultaneously to spare normal tissues in the region from potentially damaging radiation exposure. However, the results were not in favour of IORT in the case of pancreatic cancer in locally advanced and metastatic stages. There is no clear evidence to indicate the IORT as more effective than other therapies in treating pancreatic cancer.

Site impact on colorectal cancer biological behavior in terms of clinicopathological and molecular features.

PURPOSE: We investigated the biological behavior of proximal and distal colorectal adenocarcinomas (CRC), intending to determine specific segmental differences, possibly arising from the distinct genetic pathways involved in their development. METHODS: Thirty-six proximal and 83 distal cancers were comparatively and retrospectively analyzed, regarding tumor stage, grade and Ki-67, p53 and Bcl-2 immunohistochemical expression. RESULTS: Proximal tumors were more likely to be poorly differentiated (p=0.005) and to exhibit low Ki-67 and p53 expression (<20% and ≤ 30% stained nuclei respectively; p=0.026 and 0.0014, respectively). Distal lesions were more likely to be moderately differentiated (p=0.001), to display moderate Ki-67 expression (20-50% stained nuclei, p= 0.013) and p53 staining higher than 30% stained nuclei (p= 0.0014). Such segmental variations regarding mainly p53 and to a lesser extent Ki-67 were seen within most of the specific sub-groups of patients (stratified by stage, grade, gender and age). An association between Bcl-2 expression and distal site was also observed among females (p=0.008). CONCLUSION: Proximal and distal cancers displayed different clinicopathological and molecular patterns, reinforcing the proposal that they are genetically and biologically different entities. Potential clinical applications of these findings should be investigated.

Prognostic significance of p53 and Ki67 proteins expression in Greek gastric cancer patients.

AIM: The variability of prognosis of gastric cancer (GC) within a pathological stage necessitates the identification of subgroups of patients with a more aggressive disease. The role of p53 and Ki67 expression in gastric carcinoma is far from being fully established. The aim of the present study was to evaluate the expression of p53 and Ki67 in gastric cancer and correlate the findings with several clinicopathological features and prognosis. MATERIALS AND METHODS: Tissue samples from 93 patients treated by gastric resection for gastric carcinoma between 1996 and 2001 were used. Formalin-fixed paraffin-embedded tumors were studied by immunohistochemistry, using monoclonal antibodies to p53 and Ki67. The results were correlated with clinicopathological features and survival. RESULTS: Stronger expression of p53 was related with tumor size greater than 5 cm and advanced stage. Stronger expression of Ki67 correlated with higher ratio of the number of metastatic lymph nodes to the total number of dissected lymph nodes (metastatic lymph node [MLN] ratio) and advanced stage. Moreover, p53 and Ki67 overexpression, tumor size greater than 5 cm, MLN ratio, depth of invasion, lymph node metastasis, stage III and IV and infiltrative macroscopic appearance were adverse prognostic factors. The levels of p53 and Ki67, the MLN ratio, the tumor size (above 5 cm) and the stage of the disease were identified as independent prognostic factors of survival. CONCLUSIONS: In gastric cancer, the expression of p53 and Ki67 provides significant information about prognosis. The routine evaluation of p53 and Ki67 levels could be a useful tool in identification of patient with more aggressive disease and contribute to a better therapeutic approach.

Vascular complications in renal transplantation: a single-center experience in 1367 renal transplantations and review of the literature.

Renal transplantation is the treatment of choice for end-stage renal disease. Vascular complications in renal transplantation are not uncommon and may often lead to allograft loss. The most common vascular complications are transplant renal artery stenosis, transplant renal artery thrombosis, transplant renal vein thrombosis, biopsy-induced vascular injuries, pseudoaneurysm formation, and hematomas. Transplant renal artery and vein thrombosis have an early onset and a dramatic clinical manifestation and usually lead to allograft loss. In contrast, transplant renal artery stenosis has better treatment possibilities, whereas the rest do not occur so often. In our institution, 1367 renal transplantations were performed from September 1980 to April 2005. During this period, we encountered 38 major vascular complications leading to graft loss and 19 transplant renal artery stenoses with successful treatment in the majority of cases. According to these data, we can conclude that renal transplantation is a safe therapeutic procedure for renal failure.

Laparoscopic bowel injury: role of the site and the instrument type: study with an animal model.

BACKGROUND: Unrecognized laparoscopic bowel injuries are complications that can occur during any laparoscopic procedure. These complications have variable morbidity and mortality rates, and their early clinical signs of inflammation are not typical. Therefore, a study was planned to predict the mechanical behavior of the injured bowel, taking into consideration two parameters: the size of the instrument and the site of the injury. METHODS: For this study, 78 Wistar rats were divided into eight study groups and one control group with two subgroups. Bowel injury was created using different sizes of needles and electrocautery on two different bowel sites: the jejunum and the terminal ileum. The animals were killed 48 h after surgery, followed by harvesting of the injured part of the bowel and measurement of the intraluminal pressure at which the bowel ruptured. RESULTS: The mean jejunum and terminal ileum rupture pressures on the injured bowel were significantly lower than on the intact bowel. The mean terminal ileum rupture pressures were significantly lower than those of the jejunum. CONCLUSIONS: The terminal ileum appears to be more fragile than the jejunum regardless of the size of the instrument that caused the injury. However, wider instrument tips cause more serious consequences.