European clinical practice guidelines for the definition, diagnosis, and treatment of oligometastatic esophagogastric cancer (OMEC-4).

INTRODUCTION: The OligoMetastatic Esophagogastric Cancer (OMEC) project aims to provide clinical practice guidelines for the definition, diagnosis, and treatment of esophagogastric oligometastatic disease (OMD). METHODS: Guidelines were developed according to AGREE II and GRADE principles. Guidelines were based on a systematic review (OMEC-1), clinical case discussions (OMEC-2), and a Delphi consensus study (OMEC-3) by 49 European expert centers for esophagogastric cancer. OMEC identified patients for whom the term OMD is considered or could be considered. Disease-free interval (DFI) was defined as the time between primary tumor treatment and detection of OMD. RESULTS: Moderate to high quality of evidence was found (i.e. 1 randomized and 4 non-randomized phase II trials) resulting in moderate recommendations. OMD is considered in esophagogastric cancer patients with 1 organ with ≤ 3 metastases or 1 involved extra-regional lymph node station. In addition, OMD continues to be considered in patients with OMD without progression in number of metastases after systemic therapy. 18F-FDG PET/CT imaging is recommended for baseline staging and for restaging after systemic therapy when local treatment is considered. For patients with synchronous OMD or metachronous OMD and a DFI ≤ 2 years, recommended treatment consists of systemic therapy followed by restaging to assess suitability for local treatment. For patients with metachronous OMD and DFI > 2 years, upfront local treatment is additionally recommended. DISCUSSION: These multidisciplinary European clinical practice guidelines for the uniform definition, diagnosis and treatment of esophagogastric OMD can be used to standardize inclusion criteria in future clinical trials and to reduce variation in treatment.

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.

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.

Definition, diagnosis and treatment of oligometastatic oesophagogastric cancer: A Delphi consensus study in Europe.

BACKGROUND: Local treatment improves the outcomes for oligometastatic disease (OMD, i.e. an intermediate state between locoregional and widespread disseminated disease). However, consensus about the definition, diagnosis and treatment of oligometastatic oesophagogastric cancer is lacking. The aim of this study was to develop a multidisciplinary European consensus statement on the definition, diagnosis and treatment of oligometastatic oesophagogastric cancer. METHODS: In total, 65 specialists in the multidisciplinary treatment for oesophagogastric cancer from 49 expert centres across 16 European countries were requested to participate in this Delphi study. The consensus finding process consisted of a starting meeting, 2 online Delphi questionnaire rounds and an online consensus meeting. Input for Delphi questionnaires consisted of (1) a systematic review on definitions of oligometastatic oesophagogastric cancer and (2) a discussion of real-life clinical cases by multidisciplinary teams. Experts were asked to score each statement on a 5-point Likert scale. The agreement was scored to be either absent/poor (<50%), fair (50%-75%) or consensus (≥75%). RESULTS: A total of 48 experts participated in the starting meeting, both Delphi rounds, and the consensus meeting (overall response rate: 71%). OMD was considered in patients with metastatic oesophagogastric cancer limited to 1 organ with ≤3 metastases or 1 extra-regional lymph node station (consensus). In addition, OMD was considered in patients without progression at restaging after systemic therapy (consensus). For patients with synchronous or metachronous OMD with a disease-free interval ≤2 years, systemic therapy followed by restaging to consider local treatment was considered as treatment (consensus). For metachronous OMD with a disease-free interval >2 years, either upfront local treatment or systemic treatment followed by restaging was considered as treatment (fair agreement). CONCLUSION: The OMEC project has resulted in a multidisciplinary European consensus statement for the definition, diagnosis and treatment of oligometastatic oesophagogastric adenocarcinoma and squamous cell cancer. This can be used to standardise inclusion criteria for future clinical trials.

Definitions and treatment of oligometastatic oesophagogastric cancer according to multidisciplinary tumour boards in Europe.

BACKGROUND: Consensus about the definition and treatment of oligometastatic oesophagogastric cancer is lacking. OBJECTIVE: To assess the definition and treatment of oligometastatic oesophagogastric cancer across multidisciplinary tumour boards (MDTs) in Europe. MATERIAL AND METHODS: European expert centers (n = 49) were requested to discuss 15 real-life cases in their MDT with at least a medical, surgical, and radiation oncologist present. The cases varied in terms of location and number of metastases, histology, timing of detection (i.e. synchronous versus metachronous), primary tumour treatment status, and response to systemic therapy. The primary outcome was the agreement in the definition of oligometastatic disease at diagnosis and after systemic therapy. The secondary outcome was the agreement in treatment strategies. Treatment strategies for oligometastatic disease were categorised into upfront local treatment (i.e. metastasectomy or stereotactic radiotherapy), systemic therapy followed by restaging to consider local treatment or systemic therapy alone. The agreement across MDTs was scored to be either absent/poor (<50%), fair (50%-75%), or consensus (≥75%). RESULTS: A total of 47 MDTs across 16 countries fully discussed the cases (96%). Oligometastatic disease was considered in patients with 1-2 metastases in either the liver, lung, retroperitoneal lymph nodes, adrenal gland, soft tissue or bone (consensus). At follow-up, oligometastatic disease was considered after a median of 18 weeks of systemic therapy when no progression or progression in size only of the oligometastatic lesion(s) was seen (consensus). If at restaging after a median of 18 weeks of systemic therapy the number of lesions progressed, this was not considered as oligometastatic disease (fair agreement). There was no consensus on treatment strategies for oligometastatic disease. CONCLUSION: A broad consensus on definitions of oligometastatic oesophagogastric cancer was found among MDTs of oesophagogastric cancer expert centres in Europe. However, high practice variability in treatment strategies exists.

Precision Medicine in Aortic Anastomosis: A Numerical and Experimental Study of a Novel Double-Sided Needle.

BACKGROUND: Hand-sewn anastomosis is a crucial part of aortic reconstruction surgery and significantly affects its outcome. The present study presents a novel, bidirectional surgical needle aimed to improve aortic anastomosis in terms of speed and ease of use. Our objective was to assess the efficacy of the new design in comparison with the conventional needle. METHODS: A series of simulations were conducted with COMSOL software in order to perform a fatigue comparative analysis between the new and the conventional needle design. Ease of penetration into a piece of polydimethylsiloxane was evaluated. Lastly, the prototype was tested under in-vitro conditions in comparison with the conventional needle. RESULTS: Based on fatigue analysis, the new needle design improves durability, provided the two tips are equally used. The polytetrafluoroethylene coating improves penetration into the tissue by 7% to 17%, while electropolishing improves penetration up to 19%. When using the novel needle design, the average anastomotic task completion time was significantly reduced by 22% and the overall distance of hand movements was significantly reduced by 20%. CONCLUSIONS: The proposed design exhibited a shorter anastomotic time and seems promising in relation to ease of use and simplicity of the anastomotic technique it introduces.

Surgery for metachronous oligometastatic esophageal cancer: Is there enough evidence? / Cirugía para el cáncer de esófago oligometastásico metacrónico: ¿hay suficiente evidencia?

Esophageal cancer is the sixth most common cause of cancer-related mortality worldwide. Despite advances in diagnostic modalities and treatment options, five-year survival rates are below 20%. Esophagectomy with extended lymph node dissection is the mainstay of treatment. More than 50% of patients experience recurrence within 1-3 years postoperatively. Recurrent disease may present locoregionally at the site of anastomosis or as recurrence through lymphatic spread in lymph node basins, as hematogenic metastasis, or as a combination of these. The standard treatment of recurrence is currently predicated on systemic chemotherapy and/or radiotherapy. Recent evidence suggests that surgical treatment of metachronous oligometastatic disease may be prognostically advantageous over medical management alone. Given the considerably low response rates to chemoradiotherapy, many institutions have adopted surgical treatment strategies for oligo-recurrent disease on a case-by-case basis. The aim of this article is to review the current evidence on the role of surgical treatment for metachronous oligometastases from esophageal cancer. (AU)

El cáncer de esófago es la sexta causa más frequente de mortalidad relacionada con el cáncer en todo el mundo. A pesar de los avances en los medios de diagnóstico y las opciones de tratamiento, la tasa de supervivencia a los cinco años es menor del 20%. La esofagectomía con la disección de ganglios linfáticos extendida es la base del tratamiento. Más del 50% de los pacientes experimentan recurrencia dentro de 1-3 años después de la operación. La enfermedad recurrente puede presentarse como recidiva locorregional en el sitio de la anastomosis o como recidiva a través de diseminación en los ganglios linfáticos, como metástasis hematológicas o como una combinación de todos ellos. El tratamiento estándar de la recidiva se basa actualmente en la quimioterapia sistémica y/o radioterapia. La evidencia reciente sugiere que el tratamiento quirúrgico de la enfermedad oligometastásica metacrónica puede tener ventajas pronósticas superiores al tratamiento exclusivamente médico. Dada la tasa de respuesta considerablemente baja a la quimiorradioterapia, muchas instituciones han adoptado estrategias de tratamiento quirúrgico para la enfermedad oligorrecurrente caso por caso. El objetivo de este artículo es revisar la evidencia actual sobre el papel del tratamiento quirúrgico de las oligometástasis metacrónicas del cáncer de esófago. (AU)

Surgery for metachronous oligometastatic esophageal cancer: Is there enough evidence?

Esophageal cancer is the sixth most common cause of cancer-related mortality worldwide. Despite advances in diagnostic modalities and treatment options, five-year survival rates are below 20%. Esophagectomy with extended lymph node dissection is the mainstay of treatment. More than 50% of patients experience recurrence within 1-3 years postoperatively. Recurrent disease may present locoregionally at the site of anastomosis or as recurrence through lymphatic spread in lymph node basins, as hematogenic metastasis, or as a combination of these. The standard treatment of recurrence is currently predicated on systemic chemotherapy and/or radiotherapy. Recent evidence suggests that surgical treatment of metachronous oligometastatic disease may be prognostically advantageous over medical management alone. Given the considerably low response rates to chemoradiotherapy, many institutions have adopted surgical treatment strategies for oligo-recurrent disease on a case-by-case basis. The aim of this article is to review the current evidence on the role of surgical treatment for metachronous oligometastases from esophageal cancer.

Risk Models and Scores in Patients with Peripheral Artery Disease and Chronic Limb-threatening Ischemia: A Comprehensive Review.

Peripheral artery disease (PAD) affects more than 200 million patients worldwide and chronic limbthreatening ischemia (CLTI) is the most advanced stage of PAD with very high morbidity and mortality rates. Cardiovascular medicine is trending towards a more personalized approach where each individual patient will be managed according to specific risk factors, disease characteristics, expectations related to their disease and individualized assessment of potential outcomes. For this reason, a number of risk models and scores have been developed during the last few years. Our aim in this comprehensive review article is to provide an overview of selected risk models and scores for patients with PAD and CLTI. Given that some of the published scores were of low quality (minimal discriminatory ability), we included scores that were already externally validated or scores that had promising initial findings. Available scoring systems were grouped in the five following categories according to their utility: i) scores that can detect asymptomatic patients who should be screened for PAD, ii) scores for assessment of functional status and quality of life in patients with PAD, iii) scores assessing risk for amputation and other major adverse limb events among patients with CLTI, iv) scores for the optimal revascularization strategy in each patient and scores predicting successful procedural outcomes; v) scores predicting short or long-term cardiovascular and limb related outcomes after either revascularization or at least angiographic assessment. Limitations of available scoring systems include development and validation in specific populations, lack of external validation (for some of them) and also lack of synchrony with current era endovascular technology. However, with further optimization of current scores and the development of new scores, the field of PAD and CLI can be transitioned to a personalized medicine approach.

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.

Human Papilloma Virus infection and breast cancer development: Challenging theories and controversies with regard to their potential association.

Breast cancer (BC) remains the most frequently diagnosed malignancy among women worldwide. Recognized predisposing factors may be absent in the majority of affected patients, which has aroused a stronger interest in identifying risk parameters that contribute to BC pathogenesis. Human papilloma virus (HPV) infection is strongly associated with malignancies, such as cervical cancer, oropharyngeal cancer and anal cancer. Various surveys have linked HPV to the development of BC. Relevant variations in HPV identification among BC samples may be attributed to differences in study design, the populations involved and the HPV detection techniques applied, which are still controversial with conflicting opinions and results that deny the causative association between HPV infection and BC development. Furthermore, the role of HPV, a potential cause of human BC, has recently received more attention because of the possible restriction of disease progression using an HPV vaccine. The aim of this review was to evaluate both the aspects supporting and those against the theory of BC related to HPV infection. Recent literature has been also assessed in order to provide an update on the current concepts of relevant association.

Prognostic factors affecting mortality in patients with esophageal GISTs.

PURPOSE: Esophageal gastrointestinal stromal tumors (GISTs) compose a very rare clinical entity, representing 0.7% of all GISTs. Therefore, the clinicopathological factors that affect mortality are currently not adequately examined. We reviewed individual cases of esophageal GISTs found in the literature in order to identify the prognostic factors affecting mortality. METHODS: MEDLINE, EMBASE, and the Cochrane Library were systematically searched to identify clinical studies and case reports referring to esophageal GISTs. The clinicopathological features were recorded and evaluated. RESULTS: A total number of 105 patients were found. The median age of patients was 58 years (mean 52.4%). The majority of patients (71.6%) presented with tumor-associated symptoms. Tumors were mostly located at the lower esophagus (72.9%), and the median tumor size was 7 cm. Esophagectomy was the most common surgical approach (54.3%), followed by tumor enucleation (45.7%). The median follow-up period was 34 months; tumor recurrence occurred in 18 cases (18.9%) and 19 died of disease (19.2%). The overall survival rate was 75.8%. We found out that tumor size and high mitotic rate (>10 mitosis per hpf) were significant prognostic factors for survival. Presence of symptoms, ulceration, and tumor necrosis as well as tumor recurrence were also significant prognostic factors (p<0.01). CONCLUSIONS: Esophageal GISTs' tumor size and mitotic rate are the most significant factors for survival. For dubious cases, a pre-operative biopsy can auspiciously establish the diagnosis of an esophageal GIST. Regarding surgical treatment, tumor enucleation can be safely and feasibly performed for relatively small, intact tumors, whereas large, aggressive tumors are resected with radical esophagectomy.

Immunotherapy for esophageal cancer: a 2019 update.

Esophageal cancer remains a global health concern with a dismal prognosis and an estimated 5-year survival rate of approximately 10-15%. Immunotherapy is a novel treatment approach representing an effective and promising option against several types of cancer. The development of new and efficacious immunotherapeutic strategies, such as adoptive cell therapy-based, antibody-based and vaccine-based therapies, aims to prevent immunological escape and modify immunological responses. In this review, we discuss the theoretical background and current status of immunotherapy for patients with esophageal cancer. We also present ongoing clinical trials and summarize key findings concerning survival and safety analyses.

Acute esophageal necrosis: A systematic review and pooled analysis.

BACKGROUND: Acute esophageal necrosis (AEN) is a rare entity with multifactorial etiology, usually presenting with signs of upper gastrointestinal bleeding. AIM: To systematically review all available data on demographics, clinical features, outcomes and management of this medical condition. METHODS: A systematic literature search was performed with respect to the PRISMA statement (end-of-search date: October 24, 2018). Data on the study design, interventions, participants and outcomes were extracted by two independent reviewers. RESULTS: Seventy-nine studies were included in this review. Overall, 114 patients with AEN were identified, of whom 83 were males and 31 females. Mean patient age was 62.1 ± 16.1. The most common presenting symptoms were melena, hematemesis or other manifestations of gastric bleeding (85%). The lower esophagus was most commonly involved (92.9%). The most widely implemented treatment modality was conservative treatment (75.4%), while surgical or endoscopic intervention was required in 24.6% of the cases. Mean overall follow-up was 66.2 ± 101.8 d. Overall 29.9% of patients died either during the initial hospital stay or during the follow-up period. Gastrointestinal symptoms on presentation [Odds ratio 3.50 (1.09-11.30), P = 0.03] and need for surgical or endoscopic treatment [surgical: Odds ratio 1.25 (1.03-1.51), P = 0.02; endoscopic: Odds ratio 1.4 (1.17-1.66), P < 0.01] were associated with increased odds of complications. A sub-analysis separating early versus late cases (after 2006) revealed a significantly increased frequency of surgical or endoscopic intervention (9.7 % vs 30.1% respectively, P = 0.04). CONCLUSION: AEN is a rare condition with controversial pathogenesis and unclear optimal management. Although the frequency of surgical and endoscopic intervention has increased in recent years, outcomes have remained the same. Therefore, further research work is needed to better understand how to best treat this potentially lethal disease.

The impact of cirrhosis on esophageal cancer surgery: An up-to-date meta-analysis.

AIM: The incidence of esophageal malignancies is higher in cirrhotic patients due to the fact that cirrhosis and esophageal cancer share common risk factors. Our goal was to define the impact of cirrhosis on postoperative outcomes following esophagectomy for esophageal cancer. METHODS: This study was performed according to the PRISMA guidelines. Eligible studies were identified through search of PubMed, Scopus, and Cochrane (end-of-search date: March 8th, 2019). A meta-analysis was conducted using random effects modeling. RESULTS: We included 12 observational studies reporting on a total of 1938 patients who underwent surgery for esophageal cancer. Cirrhotic patients were more likely to develop postoperative pulmonary complications (OR: 2.60; 95% CI: 1.53-4.42), ascites (OR: 37.77; 95% CI: 10.95-130.28) and anastomotic leak/fistula within 30 days (OR: 2.81; 95% CI: 1.05-7.49) after esophageal cancer surgery. Cirrhotic patients had higher 30-day (OR: 3.04; 95% CI: 1.71-5.39) mortality rate. Liver disease did not appear to influence 90-day (OR: 2.84; 95% CI: 0.94-8.93) or late mortality rates (at a mean of 24 months of postoperative follow up) (OR: 1.70; 95% CI: 0.53-5.51). Esophagectomy for carcinoma in Child-Turcotte-Pugh class A cirrhotic patients was associated with significantly lower 30-day mortality rates compared to class B patients (OR: 0.14; 95% CI: 0.04-0.54). CONCLUSIONS: Cirrhotic patients have higher odds of developing pulmonary complications, ascites, and anastomotic leak during the first postoperative month. Although, 30-day mortality was higher among cirrhotic patients after esophagectomy, liver disease does not seem to influence long-term prognosis.

Primary Angiosarcoma of the Kidney: Literature Review of a Rare Nosologic Entity.

Primary angiosarcoma of the kidney is a rare tumor, hence little is known concerning its diagnostic features and therapeutic management. We conducted this survey to present a complete literature review with emphasis on clinicopathological features, diagnosis and therapy. A thorough search was conducted in MEDLINE/PubMed. All relevant studies concerning primary renal angiosarcomas in adults were thoroughly reviewed. Primary renal angiosarcoma is characterized by an overall poor prognosis, is of unknown etiology and occurs most commonly in males between 60 and 70 years old. Presence of distant metastasis at the time of diagnosis is prevalent. Histopathological examination and immunohistochemical studies are the most important diagnostic tools. Treatment options include surgery, chemotherapy, radiotherapy and immunotherapy. Conclusion: Primary renal angiosarcoma is a rare but aggressive malignancy with low response to available therapeutic regimens and dismal survival rates.

LINX® reflux management system to bridge the "treatment gap" in gastroesophageal reflux disease: A systematic review of 35 studies.

BACKGROUND: Gastroesophageal reflux disease (GERD) occurs when the reflux of stomach contents causes troublesome symptoms and/or complications. When medical therapy is insufficient, surgical therapy is indicated and, until now, Laparoscopic fundoplication (LF) constitutes the gold-standard method. However, magnetic sphincter augmentation (MSA) using the LINX® Reflux Management System has recently emerged and disputes the standard therapeutic approach. AIM: To investigate the device's safety and efficacy in resolving GERD symptoms. METHODS: This is a systematic review conducted in accordance to the PRISMA guidelines. We searched MEDLINE, Clinicaltrials.gov, EMBASE, Cochrane Central Register of Controlled Trials CENTRAL databases from inception until September 2019. RESULTS: Overall, 35 studies with a total number of 2511 MSA patients were included and analyzed. Post-operative proton-pump inhibitor (PPI) cessation rates reached 100%, with less bloating symptoms and a better ability to belch or vomit in comparison to LF. Special patient groups (e.g., bariatric or large hiatal-hernias) had promising results too. The most common postoperative complication was dysphagia ranging between 6% and 83%. Dilation due to dysphagia occurred in 8% of patients with typical inclusion criteria. Esophageal erosion may occur in up to 0.03% of patients. Furthermore, a recent trial indicated MSA as an efficient alternative to double-dose PPIs in moderate-to-severe GERD. CONCLUSION: The findings of our review suggest that MSA has the potential to bridge the treatment gap between maxed-out medical treatment and LF. However, further studies with longer follow-up are needed for a better elucidation of these results.

Minimally Invasive Esophagectomy.

Minimally invasive esophagectomy (MIE) was introduced in the 1990s with the aim to decrease the rate of respiratory complications associated with thoracotomy, along with the benefits of reduced morbidity and a quicker return to normal activities provided by minimally invasive techniques. However, MIE is not routinely applied as a standard approach for esophageal cancer worldwide, due to the high technical complexity of this minimally invasive procedure. Therefore, the open transthoracic esophagectomy is considered to be the gold standard for resectable esophageal cancer worldwide nowadays. In this article, the current status of conventional MIE and robot-assisted minimally invasive thoraco-laparoscopic esophagectomy will be reviewed.

Histone Deacetylases (HDACs) in Gastric Cancer: An Update of their Emerging Prognostic and Therapeutic Role.

Chemotherapy resistance is a rising concern in Gastric Cancer (GC) and has led to the investigation of various cellular compounds. Α functional equilibrium of histone acetylation and deacetylation was discovered in all cells, regulated by Histone Acetyltransferases and Deacetylases (HDACs), controlling chromatin coiling status and changing gene expression appropriately. In accordance with recent research, this equilibrium can be dysregulated in cancer cells aiding in the process of carcinogenesis and tumor progression by altering histone and non-histone proteins affecting gene expression, cell cycle control, differentiation, and apoptosis in various malignancies. In addition, increased HDAC expression in GC cells has been associated with increased stage, tumor invasion, nodal metastases, increased distant metastatic potential, and decreased overall survival. HDAC inhibitors could be used as treatment regimens for GC patients and could develop important synergistic interactions with chemotherapy drugs. The aim of this article is to review the molecular identity and mechanism of action of HDAC inhibitors, as well as highlight their potential utility as anti-cancer agents in GC.