Associations of long non-coding RNAs HOTAIR, LINC00951, POLR2E and HULC polymorphisms with the risk of esophageal and esophagogastric junction cancer in a western population: a case-control study.

BACKGROUND: The incidence of single-nucleotide-polymorphisms with malignant potential in esophageal cancer tissues has only been sparsely investigated in the west. Hence, we explored the contribution of four long non-coding RNAs' polymorphisms HOTAIR rs920778, LINC00951 rs11752942, POLR2E rs3787016 and HULC rs7763881 in esophageal cancer susceptibility. METHODS AND RESULTS: Formalin-fixed paraffin-embedded tissue specimens from 95 consecutive patients operated for esophageal/esophagogastric junction carcinoma during 25/03/2014-25/09/2018 were processed. Demographic data, histopathological parameters, surgical and oncological outcomes were collected. DNA findings of the abovementioned population were compared with 121 healthy community controls. Both populations were of European/Greek ancestry. Sixty-seven patients underwent Ivor Lewis/McKeown esophagectomy for either squamous cell esophageal carcinoma (N = 6) or esophageal/esophagogastric junction Siewert I or II adenocarcinoma (N = 61). Twenty-eight patients were subjected to extended total gastrectomy for esophagogastric junction Siewert III adenocarcinoma. Neither LINC00951 rs11752942 nor HULC rs7763881 polymorphisms were detected more frequently in esophageal cancer patients compared with healthy community subjects. A significantly higher presence of HOTAIR rs920778 TT genotype in esophagogastric junction Siewert I/II adenocarcinoma was identified. POLR2E rs3787016 C allele and CC genotypes were overrepresented in the control group, and when found in esophageal cancer carriers were associated with earlier disease stages, as well as with minor lymph node involvement and lesser metastatic potential. CONCLUSIONS: HOTAIR rs920778 may serve as a potential therapeutic suppression target, while POLR2E rs3787016 may represent a valuable biomarker to evaluate esophageal cancer predisposition and predict treatment response and prognosis. Clinical implications of these findings need to be verified with further prospective studies with larger sample-size.

Genetic Impact of HOTAIR, LINC00951, POLR2E and HULC Polymorphisms in Histopathological and Laboratory Prognostic Factors in Esophageal Cancer in the West: A Case-Control Study.

Long non-coding RNAs' HOTAIR rs920778, LINC00951 rs11752942, POLR2E rs3787016, and HULC rs7763881 are progressively reported having a close genetic affinity with esophageal carcinogenesis in the East. Nonetheless, their correlation with variables already endorsed as significant prognostic factors in terms of staging, guiding treatment and predicting recurrence, metastasis, and survival have yet to be explored. Herein, we investigated their prognostic value by correlating them with clinicopathological and laboratory prognostic markers in esophageal cancer in the West. Formalin-fixed paraffin-embedded tissue specimens from 95 consecutive patients operated on for esophageal cancer between 2014 and 2018 were compared with 121 healthy community controls. HULC was not detected differently in any of the cancer prognostic subgroups. LINC00951 was underrepresented in Ca19.9 elevated subgroup. HOTAIR was more frequent in both worse differentiation grade and positive Signet-Ring-Cell and Ca19.9 subgroups. POLR2E was identified less frequently in Adenocarcinoma, Signet-Ring-Cell, and Diffuse histologies, as well as in Perineural, Lymphovascular, and Perivascular Invasion positive, while it was overrepresented in CEA positive subgroup. These lncRNAs polymorphisms may hold great potential not only as future therapeutic agents but also as novel markers for predictive analysis of esophageal cancer risk, clinical outcome, and survival. Clinical implications of these findings need to be validated with prospective larger sample-size studies.

Alexander the Great (356-323 BC) and His Injury in Kyropolis Reconsidered.

Purpose: To reconsider Alexander the Great's injury in Kyropolis. Methods: Historical sources were compared with modern neurosurgery. Results: Earlier interpretations were focused on the transient blindness Alexander the Great presented after the injury, but according to our point of view we should rather focus on his dysarthria which lasted almost two months. Conclusion: We propose the hypothesis that Alexander the Great developed a posttraumatic delayed cerebellar syndrome after the injury.

Clinical and Oncological Impact of the Toll-like Receptor-3 and -4 in Esophageal and Gastro-esophageal Junction Adenocarcinoma.

BACKGROUND/AIM: Esophageal and gastro-esophageal junction cancer is a major cause of cancer-related mortality, with poor prognosis. Toll-like receptors (TLRs) play a significant role in the innate immune system; their increased expression has been associated with esophageal adenocarcinoma. This study aimed to determine the association between TLR-3 and TLR-4 expression with clinical and oncological outcomes of patients that underwent esophagectomy for cancer. PATIENTS AND METHODS: This is a retrospective analysis of prospectively collected data from consecutive patients within a 2-year period. Primary endpoints of the study were the assessment of the expression of TLR-3 and TLR-4 in primary tumors as well as in metastatic lymph nodes. Secondary endpoints were the correlation of TLR-3 and TLR-4 values with the clinical, pathological, and oncological outcomes. RESULTS: A significantly higher expression of TLR-3 and TLR-4 in primary tumors and metastatic-lymph nodes was observed. There was a significant association between TLR-3 expression and T-stage, as well as TLR-4 expression and grade of differentiation in the primary site. Additionally, metastatic-lymph node TLR-4 expression was significantly correlated with N-stage. A strong correlation between TLR-4 expression and overall or progression-free survival rates was detected. CONCLUSION: This study found a significantly increased TLR expression in malignant tissue/metastatic lymph nodes, as well as a significant positive correlation between TLRs and worse clinical outcomes. TLRs have a pivotal role in the inflammation pathway in the esophagus and during esophageal carcinogenesis. This study highlights the need for further investigation into TLR-mediated signaling pathways and their potential role as diagnostic and therapeutic targets.

Impact of Minimally Invasive Intrathoracic Hand-sewn Esophago-gastric Anastomosis in Esophagectomy for Cancer.

BACKGROUND/AIM: Ivor Lewis esophagectomy is considered the gold standard approach for the treatment of distal esophageal and gastro-esophageal junction Siewert I-II tumors. Minimally invasive esophagectomy has provided improved outcomes compared to the open approach, offering reduced morbidity, and improved clinical and oncological outcomes. This is the largest study so far reporting the impact of hand-sewn esophago-gastric anastomosis in the prone position, during the 2-stage totally minimally invasive esophagectomy. PATIENTS AND METHODS: A retrospective analysis of prospectively collected data regarding consecutive patients with distal-esophageal and gastroesophageal junction Siewert I-II tumors was conducted. All patients underwent 2-stage totally minimally invasive esophagectomy with thoracoscopic manual esophago-gastric anastomosis in the prone position. Clinical and oncological outcomes were examined and presented. RESULTS: One hundred and fifty consecutive patients were included in the study during a period of five years. Median operative time was 320 minutes, while median time for the construction of anastomosis was 45 minutes. We had no conversions to open esophagectomy. Anastomotic leakage was observed in 2% of the patients; anastomotic stricture rate reached up to 7.33%. Respiratory complications were seen in 18% and cardiac complications in 6.66% of the patients, respectively. Thirty-day mortality and 90-day mortality rates were 1.33% and 2.66%, accordingly. CONCLUSION: Intrathoracic hand-sewn esophago-gastric anastomosis in the prone position during totally minimally invasive esophagectomy has provided favorable outcomes in our cohort of patients, offering significantly reduced anastomotic-related complications, compared to other standardized techniques. Further prospective comparative studies are needed, to better interpret and amplify our results, that may lead to a paradigm shift regarding the preferred method of reconstruction from esophageal surgeons.

The Role of Toll-like Receptors in Esophageal Cancer.

Esophageal adenocarcinoma (AC) develops through Barrett's esophagus (BE) and columnar dysplasia, preceded by gastro-esophageal reflux disease (GERD). Incidence of esophageal squamous cell carcinoma (SCC) is increased with tobacco smoking and alcohol abuse. Toll-like receptors (TLRs) can act as prognostic factors and potential therapeutic targets of esophageal cancer. TLRs, an important family of pattern recognition receptors, allow immune cells to recognize pathogens triggering inflammation. TLR-signaling pathway activates signaling-elements, regulating inflammatory response, possibly correlating to carcinogenesis. In the normal esophagus, TLRs recognize molecular patterns on microorganisms and inflammatory response produced by tissue-damage. TLR3, TLR4, TLR5, and TLR9 are expressed at increasing levels from GERD to AC. TLR4 is a mediator of proliferation in AC, while TRL1 and TLR4 over-expression in AC is related to poor prognosis and metastasis. Additionally, TLR3, TLR4, and TLR9 expression in SCC has been associated with lymphatic metastasis, whereas increased expression of TLR7 and TLR9 has been also associated with advanced disease. It seems that TLR expression can indicate esophageal metaplasia, dysplasia, and cancer. Herein, we aimed to present all available data regarding the relation of TLRs and esophageal cancer. They may represent significant and valuable diagnostic or prognostic factors for esophageal cancer.

Role and Efficacy of Robotic-assisted Radical Antegrade Modular Pancreatosplenectomy (RAMPS) in Left-sided Pancreatic Cancer.

Distal pancreatectomy with splenectomy is the gold-standard surgery for the treatment of left-sided pancreatic cancer. Margin negative resection accompanied by effective lymphadenectomy are the deciding factors affecting the outcome of tail-body pancreatic adenocarcinoma. Radical antegrade modular pancreatosplenectomy (RAMPS) is considered as a reasonable approach for margin-negative and systemic lymph node clearance. Herein, we aim to present all existing data regarding this novel approach including surgical technique and comparison with standardized procedures. RAMPS has shown oncological superiority comparing to distal pancreatectomy with splenectomy due to radical lymphadenectomy and improved dissection of the posterior pancreatic aspects. Robotic-assisted RAMPS has recently been described as a valuable alternative to open RAMPS. With this novel technique, anterior, posterior or modified approaches can be achieved; favorable clinical and oncological outcomes have been reported in the current literature, with reduced conversion rates compared to other minimally invasive approaches, as well as vastly improved maneuverability, accuracy and vision. Robotic-assisted RAMPS is not only technically feasible but also oncologically safe in cases of well-selected, left-sided pancreatic cancer.

Minimally Invasive Transcervical Esophagectomy With Mediastinal Lymphadenectomy for Cancer. A Comparison With Standardized Techniques.

Pulmonary complications remain the most common problem following transthoracic esophagectomy. Minimally invasive approach has significantly improved clinical outcomes; however, respiratory distress is still significant. Minimally invasive transcervical esophagectomy with mediastinal lymphadenectomy avoids thoracic access, which may decrease pulmonary complications. Transcervical esophagectomy refers to transcervical esophageal mobilization and mediastinal lymphadenectomy followed by a transhiatal gastric and distal-esophageal mobilization, abdominal and lower mediastinal lymphadenectomy. Adoption of innovative minimally invasive techniques for the transcervical or transhiatal approach, such as laparoscopy or robotic-assisted mediastinoscopy have made possible transmediastinal approach for radical esophagectomy. This novel approach with avoidance of thoracotomy or thoracoscopy can omit one lung ventilation as in transthoracic esophagectomy. Patients with previous thoracic surgery, impaired respiratory system, and major comorbidities, who are unable to undergo transthoracic esophagectomy, become candidates for radical esophagectomy with promising results. Minimally invasive transcervical esophagectomy for esophageal cancer is a safe and feasible approach and may be a valuable alternative with promising clinical and oncological outcomes.

Revision of Roux-en-Y Gastric Bypass for Inadequate Weight Loss or Weight Regain.

Inadequate weight loss or weight regain after Roux-en-Y gastric bypass (RYGBP) occurs in more than a quarter of patients for various reasons. Available remedying treatment options include endoscopic and surgical techniques for revision of the gastric pouch and the gastro-jejunal anastomosis, conversion of standard to distal gastric bypass (DRYGBP) or the conversion of RYGBP to biliopancreatic diversion (BPD) or duodenal switch (DS). There is quite a variability concerning the technical simplicity, safety, and effectiveness of these techniques and the small number of patients in the numerous single-center reports precludes any meaningful comparisons. This review aimed to describe all available methods and present the advantages and disadvantages of each of them, to facilitate, rather than guide, the decision of the average bariatric surgeon who encounters such a patient.

Primary angiosarcoma of aorta: A systematic review.

PURPOSE: To elucidate the epidemiology, anatomical, presentation, classification, pathology, investigative modalities, management and prognosis of primary angiosarcoma of the aorta. MATERIAL AND METHODS: A systematic review of literature from the database inception to January 2021 in PubMed and Embase, CINAHL and Cochrane Library in accordance to PRISMA was conducted. Retrieval and extraction was performed by two independent reviewers. The hierarchy of the evidence was assessed through the National Institute for Health and Care Excellence Checklist. Data were subjected to pooled prevalence analysis, Kaplan-Meier survival and test of probability using log-rank analysis. This review is registered with International Prospective Register of Systematic Reviews: RD42021231314. RESULTS: 82 studies with n = 123 cases met the inclusion criterion. Abdominal (45%) aorta was the commonest anatomical site with female predominance in ascending aorta (4:1) and aortic arch (2:1). The longest survival was in the ascending aorta and the shortest in the abdominal aorta [540 (interquartile range [IQR], 7-1560 days vs. 180 (IQR, 1-5730 days)], respectively. The overall median survival was 210 days (IQR, 1-5730 days) or 7 months. Lack of metastasis (47%) was a marker of longer survival (p < 0.03) irrespective of other attributes. CONCLUSION: The pathophysiology appears to be a trend of increasing fatigue, fever and weight loss associated with segmental dysfunction of the aorta projecting occlusive or destructive phenotypes. Computed tomography angiography features of volume-occupying, bulky, polypoid (intraluminal), protrusive vegetation, hyper vascular without atherosclerotic lesions are extremely suggestive of PA of the aorta at 5th and 6th decades of life.

Joseph Lister (1827-1912): A Pioneer of Antiseptic Surgery.

Joseph Lister was a prominent British surgeon and medical scientist who established the study of antisepsis. Applying Louis Pasteur's germ theory of fermentation on wound putrefaction, he promoted the idea of sterilization in surgery using carbolic acid (phenol) as an antiseptic. His method reduced the incidence of wound sepsis and gangrene, which, in turn, reduced the need for amputation. By showing how germs could be prevented from entering the wound, Lister increased the safety of surgical operations and laid the foundations for all subsequent advances in the field.

Feasibility and Short-Term Outcomes of Three-Dimensional Hand-Sewn Esophago-Jejunal Anastomosis in Completely Laparoscopic Total Gastrectomy for Cancer.

Laparoscopic total gastrectomy is on the rise. One of the most technically demanding steps of the approach is the construction of esophago-jejunal anastomosis. Several laparoscopic anastomotic techniques have been described, like linear stapler side-to-side or circular stapler end-to-side anastomosis; limited data exist regarding hand-sewn esophago-jejunal anastomosis. The study took place between January 2018 and June 2021. Patients enrolled in this study were adults with proximal gastric or esophago-gastric junction Siewert type III tumors that underwent 3D-assisted laparoscopic total gastrectomy. A hand-sewn esophago-jejunal anastomosis was performed in all cases laparoscopically. Forty consecutive cases were performed during the study period. Median anastomotic suturing time was 55 min, with intra-operative methylene blue leak test being negative in all cases. Median operating time was 240 min, and there were no conversions to open. The anastomotic leak rate and postoperative stricture rate were zero. The 30- and 90-day mortality rates were zero. Laparoscopic manual esophago-jejunal anastomosis utilizing a 3D platform in total gastrectomy for cancer can be performed with excellent outcomes regarding anastomotic leak and stricture rate. This anastomotic approach, although technically challenging, is safe and reproducible, with prominent results that can be disseminated in the surgical community.

A High-Cholesterol Diet Increases Toll-like Receptors and Other Harmful Factors in the Rabbit Myocardium: The Beneficial Effect of Statins.

BACKGROUND: A high-cholesterol diet (HCD) induces vascular atherosclerosis through vascular inflammatory and immunological processes via TLRs. The aim of this study is to investigate the mRNA expression of TLRs and other noxious biomarkers expressing inflammation, fibrosis, apoptosis, and cardiac dysfunction in the rabbit myocardium during (a) high-cholesterol diet (HCD), (b) normal diet resumption and (c) fluvastatin or rosuvastatin treatment. METHODS: Forty-eight male rabbits were randomly divided into eight groups (n = 6/group). In the first experiment, three groups were fed with HCD for 1, 2 and 3 months. In the second experiment, three groups were fed with HCD for 3 months, followed by normal chow for 1 month and administration of fluvastatin or rosuvastatin for 1 month. Control groups were fed with normal chow for 90 and 120 days. The whole myocardium was removed; total RNA was isolated from acquired samples, and polymerase chain reaction, reverse transcription PCR and quantitative real-time PCR were performed. RESULTS: mRNA of TLRs 2, 3, 4 and 8; interleukin-6; TNF-a; metalloproteinase-2; tissue inhibitor of metalloproteinase-1; tumor protein 53; cysteinyl aspartate specific proteinase-3; and brain natriuretic peptide (BNP) increased in HCD. Statins but not resumption of a normal diet decreased levels of these biomarkers and increased levels of antifibrotic factors. CONCLUSIONS: HCD increases the levels of TLRs; inflammatory, fibrotic and apoptotic factors; and BNP in the rabbit myocardium. Atherogenic diets adversely affect the myocardium at a molecular level and are reversed by statins.

An extraordinary rare anastomotic band causing food bolus obstruction following uneventful minimally invasive esophagectomy: endoscopic treatment.

The most common long-term complication post esophagectomy implicating the esophagogastric anastomosis is stricture-induced stenosis leading to late postoperative dysphagia. Herein, we present a case of a male patient readmitted to our Upper Gastrointestinal Department due to a food bolus obstruction through an anastomotic epithelial band arisen from a prior esophagogastric anastomosis performed 5 months earlier. A band transection in between two hemostatic clips placed on both sides of the band, followed by a release and fragmentation of the foreign body into several pieces led to its final transoral removal endoscopically. The patient experienced a direct resolution of his dysphagia and discharged on the same day. At 6 months follow-up, he remains symptom-free. In conclusion, endoscopic state-of-the-art techniques when combined with standard hemostatic surgical principles in a minimally invasive manner are excellent tools for the management of post-esophagectomy syndromes.

Microvascular grafting to enhance perfusion in colonic long-segment oesophageal reconstruction.

PURPOSE: Oesophagectomy with long-segment colon reconstruction is the first-line treatment when the stomach is not available. Supercharging of the newly formed conduit can improve vascular function utilizing intraoperative perfusion imaging system, following thoracoscopic oesophagectomy for distal-oesophageal and gastroesophageal junction cancer. The purpose of this study is to examine the safety and efficacy of microvascular augmentation of left colonic interposition following oesophagectomy for oesophageal cancer. METHODS: A retrospective analysis of 156 consecutive oesophagectomies between January 2016 and July 2018 was performed. All oesophagectomies involving left colon interposition with microvascular augmentation were included in the study. In all cases, oesophageal mobilization was performed thoracoscopically in prone position and the left colon was used as neo-oesophagus in an isoperistaltic fashion. Conduit perfusion was assessed with the Spy system and neck supercharging was performed using microsurgical technique. RESULTS: A total of n = 5 (3.2%) patients were identified. Two cases had delayed and 3 had immediate reconstruction. The conduit was microsurgically augmented in 3 cases with both venous and arterial anastomoses (supercharging) and in 2 cases with venous anastomosis only (superdrainage). No anastomotic leak was identified. One case developed left recurrent laryngeal nerve palsy with associated aspiration pneumonia. CONCLUSIONS: Supercharged colonic interposition is a safe way of oesophageal reconstruction when long-segment interposition graft is needed. In oesophageal cancer and in the absence of a viable stomach with intact gastroepiploic arcade, it should be considered a feasible option with favourable outcomes, when the expertise and facilities are available. Use of intraoperative perfusion imaging reveals improved conduit blood supply post-supercharging.

Completely Minimally Invasive Esophagectomy Versus Hybrid Esophagectomy for Esophageal and Gastroesophageal Junctional Cancer: Clinical and Short-Term Oncological Outcomes.

BACKGROUND: Minimally invasive surgery for resectable esophageal and gastroesophageal junctional (GEJ) cancer significantly reduces morbidity when compared with open surgery, as is evident from published landmark trials. Comparison of outcomes between hybrid esophagectomy (HE) and completely minimally invasive esophagectomy (CMIE) remains unclear. OBJECTIVE: We aimed to ascertain whether CMIE is associated with less postoperative complications compared with HE without oncological compromise. METHODS: All consecutive two-stage HEs and CMIEs performed between 2016 and 2018 were included. All procedures were performed with an intrathoracic anastomosis. Primary clinical outcomes were pulmonary infective and overall complications within 30 days of surgery, while primary oncological outcomes included overall survival (OS) and disease-free survival (DFS) at both 6 months and to date. Secondary outcomes included intraoperative variables and postoperative clinical parameters. RESULTS: Overall, 98 patients had CMIEs and 49 patients had HEs. There were no baseline differences between the two groups. Thirty-day postoperative pulmonary infection rates were lower in the CMIE group compared with the HE group (12.2% vs. 28.6%; p = 0.014), and 30-day overall postoperative complication rates were also lower following CMIE (35.7% vs. 59.2%; p = 0.007). OS and DFS were similar between the two groups at 6 months (p = 0.201 and p = 0.109, respectively). CONCLUSIONS: CMIE is associated with less pulmonary infective and overall postoperative complications compared with HE for resectable esophageal and GEJ cancer. No intergroup difference was observed regarding short-term survival and cancer recurrence in patients undergoing CMIE and HE. A randomized controlled trial comparing the two operative approaches is required to validate these findings.

Intrathoracic hand-sewn esophagogastric anastomosis in prone position during totally minimally invasive two-stage esophagectomy for esophageal cancer.

Utilization of totally minimally invasive esophagectomy for cancer is on the rise. Esophagogastric anastomosis is mechanically or robotically performed routinely; little report exists of hand-sewn esophagogastric anastomosis. This is the largest so far study with thoracoscopic hand-sewn esophagogastric anastomosis during fully minimally invasive two-stage esophagectomy for esophageal cancer in prone position. Consecutive two-stage totally minimally invasive esophagectomies for cancer were performed by one surgical team, from September 2016 to March 2019. All operations were technically identical in terms of patient positioning, surgical approach, extend of lymphadenectomy and type of anastomosis formed. Primary end points were anastomotic leak and anastomotic stricture rate, while secondary end points were 30-day and 90-day mortality rates. From the overall n = 80 patients, n = 67 were males, while n = 13 were females. Mean age was 64.6 years. Mean length of stay was n = 14 days. There were no conversions to open. Mean operating time was 420 minutes with no blood loss over 200 mL noted. Pulmonary and cardiac complication rate was 23.75% and 2.5%, respectively. Anastomotic leak rate was 2.5%. Anastomotic strictures were seen in 12.5% of cases. 30-day and 90-day mortality rate was 2.5% and 5%, respectively, with none accounted for ischemic conduit complications. Intrathoracic anastomosis in totally minimally invasive esophagectomy is challenging and accountable for most of the mortality associated with the procedure. In thoracoscopic two-stage esophagectomy, a mechanical anastomosis is usually preferred; this is believed to be due to the complexity of manual anastomosis associated with the thoracoscopic approach. We aim to present our series of completely hand-sewn intrathoracic anastomosis utilizing a totally minimally invasive approach with favorable outcomes. With this study, reproducibility of the anastomosis is shown that can potentially favor a change in the practice of esophageal surgeons worldwide.

A complex modality of achalasia, diverticulum and paraesophageal hernia treated through three-dimensional left thoracoscopy.

Herein, we report a case of a patient with recurrent dysphagia after an open transabdominal hernia repair for a Type IV paraesophageal hernia performed elsewhere. Subsequent work-up and medical records' review revealed the coexistence of a large left epiphrenic diverticulum in combination with achalasia synchronous to the recently repaired paraesophageal hernia. A three-dimensional left thoracoscopic diverticulectomy with a long esophagomyotomy was conducted under endoscopic guidance intraoperatively, with no perioperative complications. At 12 months' follow-up evaluation, the patient presents well with no documented recurrence. Cumulative experience from various medical specialties regarding esophageal motility disorders and endoscopic state-of-the-art techniques, when combined with minimally invasive surgical techniques, provide an effective management of esophageal motility syndromes, overall.

An extraordinary rare presentation of liver hydatidosis with hydatid cyst scolices.

The extraordinary finding of scolices with the characteristic hooklets may be found during the microscopic analysis in patients with cystic echinococcosis.