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.

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.

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.

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.

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.

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.

Thoracoscopic total esophagogastrectomy with supercharged colon interposition for the treatment of esophageal adenocarcinoma in situs inversus.

Background: Esophagectomy in situs inversus is challenging. With long-segment supercharged reconstruction, it becomes more perplexing and multidisciplinary surgical skills are needed. Challenges met and the surgical technique used is presented in this case report. Methods: The case of a 49-year old patient with situs inversus abdominus and a locally advanced distal esophageal adenocarcinoma extending to the stomach is presented. Results: Following neoadjuvant chemotherapy and due to inability to use the stomach as a conduit, a thoracoscopic total esophagogastrectomy with long-segment reconstruction was performed. The conduit used was the left colon and was supercharged with venous and arterial anastomoses in the neck. Conduit perfusion, as assessed by the Spy system revealed marked improvement post supercharging. No anastomotic leak was noted and oral diet was started on day 4. On day 26 the patient developed pneumonia necessitating intubation that was declined. Organ support was withheld with patient death at day 29. Conclusion: In long-segment esophageal reconstruction with supercharged colon, although thoracoscopy is feasible, laparoscopy is found unsafe. Careful preoperative planning and colon assessment via computed tomography(CT) colonography/angiography and a multidisciplinary team approach is recommended. Adjuncts to assess conduit perfusion like the Spy system are helpful. Supercharging the long colonic conduit is a way of minimizing ischemia-related complications.

Transmural migration of azygous vein Hem-O-lok clip causing food bolus 3 months following uneventful minimally invasive oesophagectomy.

BACKGROUND: Hem-o-lok clips are widely deployed in various laparoscopic and robotic operations. Their migration is not very common and majority of reported cases are limited to biliary, prostatic and vesico-urethral cases. METHODS: Herein, we would like to report the first case of transmural migration of Hem-o-lok clip from azygous vein stump following totally minimally invasive two-stage oesophagectomy for squamous cell carcinoma of the distal oesophagus, into the gastric conduit 3-months following uneventful discharge. The patient presented with 5-days history of worsening dysphagia. RESULTS: The subsequent gastroscopy revealed normal gastric conduit with two Hem-o-lok clips containing the azygous vein stump within its lumen at the level of the oesophago-gastric anastomosis, propagating a food bolus obstruction. The foreign body was successfully removed and the patient was discharged the same day without any complications at 5 months follow up. CONCLUSION: Hem-o-lok clip migration trends to be a well-established event. However, their mechanism and exact incidence remains elusive to this date. To the best of our knowledge, their migration in oesophageal cancer surgery has not been reported.

Chronic ileitis with transmural migration of ingested foreign body treated by laparoscopy.

BACKGROUND: Ingestion of foreign bodies such as fish bone or chicken bone is relatively common in adults; however, resultant transmural migration is extremely rare. METHODS: We present a case of a 79-year-old woman with chronic low-grade abdominal pain, worsening over the last 4 days. Computed tomography revealed segmental small bowel wall thickening with chronic inflammation suggestive of Crohn's ileitis and oral steroids were commenced; only later, ingestion of a foreign body was suspected. RESULTS AND CONCLUSION: At diagnostic laparoscopy, a linear foreign body resembling a wooden splinter was identified. It had partly migrated through the chronically inflamed bowel wall without causing perforation or abdominal contamination. It was removed laparoscopically without an enterotomy or bowel resection. Microscopy revealed non-viable bone, likely fish or chicken bone. The patient made an uneventful recovery and was discharged 3 days later. Herein we emphasise on the differential diagnosis and presentation of chronically ingested foreign bodies, as well as the feature of chronic ileitis with uncomplicated transmural migration of the ingested foreign body that was treated laparoscopically without an enterotomy.

Gastric conduit obstruction due to gastroduodenal compression: a new complication post-Ivor-Lewis oesophagectomy.

INTRODUCTION: Oesophagectomy for oesophageal carcinoma carries a high risk of significant morbidity and mortality. Delayed gastric emptying is a relatively common complication following this procedure. A variety of medical, surgical and endoscopic strategies have been described to manage it. The vast majority of cases are related to post-operative pyloric dysfunction and are amenable to conventional management strategies. PATIENTS AND METHODS: We present a new case of a patient with a duodenal hiatus hernia resulting in extrinsic gastroduodenal compression by the massively distended gastric conduit as a cause of gastric outlet obstruction following laparoscopic-assisted Ivor-Lewis oesophagectomy 2 years previously. RESULTS AND CONCLUSIONS: Surgical repair of the hiatus hernia restored the post-oesophagectomy anatomy and resolved this patient's symptoms where conventional management of post-oesophagectomy gastric outlet obstruction had failed on multiple occasions. Most cases of delayed gastric emptying post-oesophagectomy occur as a result of pyloric dysfunction and can be managed using a combination of prokinetics, surgical intervention or more commonly, endoscopic dilatation. Other potential causes and therefore investigative and management strategies should be considered in patients who repeatedly fail conventional management. We offer an alternative diagnosis that may be considered in these patients and present a novel approach to their investigation and management.

Role of 3D in minimally invasive esophagectomy.

PURPOSE: Two-stage minimally invasive esophagectomy (MIE) has gained popularity in the surgical treatment of esophageal cancer. MIE's limitation is embedded in the construction of intrathoracic anastomosis. Various anastomotic techniques have been reported; however, the mechanical one remains the most commonly adopted. This pilot study aims to describe an efficient, safe, and reproducible way of performing a hand-sewn intrathoracic esophagogastric anastomosis in conjunction with short-term results using 2D and 3D thoracoscopic approaches. METHODS: A total of n = 13 patients (mean age 67.4) underwent MIE for distal esophageal or gastroesophageal junction adenocarcinoma between January and September 2016. Resection was performed in prone position, and the esophagogastric anastomosis was constructed in an end-to-side manner in two layers with barbed knotless suture. A 2D thoracoscopic approach was used in n = 10 patients (77%) and a 3D approach in n = 3 (23%). RESULTS: n = 8 patients (61.5%) had neo-adjuvant chemotherapy and n = 5 (38.5%) had primary surgery. The mean operating time was 420 min, and the average length of stay was 10 days with no associated mortality. n = 1 (7.7%) developed a radiological leak that did not require an intervention. Thoracoscopic approach with the glasses-based 3D optical system using the angulating-tip 100° camera provided a far superior view for precise lymphadenectomy in combination to an efficient and safe construction of the anastomosis. CONCLUSION: The barbed knotless suturing technique in MIE is an efficient and safe method of constructing the esophagogastric anastomosis with promising short-term outcomes. A 3D thoracoscopic approach appears to be superior in performing the anastomosis to that of a 2D technique.

Laparoscopic Transduodenal Ampullectomy for a High-Grade Dysplasia Tumor.

Ampullary tumors occur rarely, and the only curative treatment is resection. The endoscopic approach is the most well-known and common treatment of choice. Open surgical resection is the usual treatment of choice in cases of unsuccessful endoscopic resection and big tumors. Although the technically challenging laparoscopic approach is not yet widespread, it is a feasible and safe method in well-selected patients. This case report focuses on the case of a 74-year-old male with high-grade dysplasia in the ampulla of Vater, who had an incomplete endoscopic resection. Therefore, we performed a laparoscopic transduodenal ampullectomy.

Right Thoracoscopic Excision of an Esophageal Bronchogenic Cyst.

Bronchogenic cysts, first described in 1859, are rare congenital cystic malformations of the respiratory tract, with an incidence of one per 42,000-68,000 hospital admissions in one hospital series. They comprise 10-15% of mediastinal tumors and between 50% and 60% of mediastinal cystic lesions. Its clinical diagnosis is often challenging due to the absence of distinct imaging features. This case report focuses on the case of a 51-year-old female who initially received a misdiagnosis of esophageal leiomyoma. Subsequently, during exploration in the operating theater, right thoracoscopy revealed the presence of an esophageal bronchogenic cyst.

Laparoscopic Treatment of a Symptomatic Young Woman With Median Arcuate Ligament Syndrome.

Median arcuate ligament syndrome (MALS), also known as Dunbar syndrome, celiac axis syndrome, or celiac artery compression syndrome, is caused by a band of tissue called the median arcuate ligament that compresses the celiac artery and sometimes the celiac plexus too. MALS does not always cause symptoms, but when symptoms occur, surgery is the treatment of choice. This case report focuses on the case of a 27-year-old woman presenting with postprandial episodes of abdominal pain and vomiting accompanied by loss of weight, which was found to be MALS.

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.

Deep Learning for Image Analysis in the Diagnosis and Management of Esophageal Cancer.

Esophageal cancer has a dismal prognosis and necessitates a multimodal and multidisciplinary approach from diagnosis to treatment. High-definition white-light endoscopy and histopathological confirmation remain the gold standard for the definitive diagnosis of premalignant and malignant lesions. Artificial intelligence using deep learning (DL) methods for image analysis constitutes a promising adjunct for the clinical endoscopist that could effectively decrease BE overdiagnosis and unnecessary surveillance, while also assisting in the timely detection of dysplastic BE and esophageal cancer. A plethora of studies published during the last five years have consistently reported highly accurate DL algorithms with comparable or superior performance compared to endoscopists. Recent efforts aim to expand DL utilization into further aspects of esophageal neoplasia management including histologic diagnosis, segmentation of gross tumor volume, pretreatment prediction and post-treatment evaluation of patient response to systemic therapy and operative guidance during minimally invasive esophagectomy. Our manuscript serves as an introduction to the growing literature of DL applications for image analysis in the management of esophageal neoplasia, concisely presenting all currently published studies. We also aim to guide the clinician across basic functional principles, evaluation metrics and limitations of DL for image recognition to facilitate the comprehension and critical evaluation of the presented 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.

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.