Improving the Diagnostic Yield of High-Resolution Esophageal Manometry for GERD: The "Straight Leg-Raise" International Study.

BACKGROUND & AIMS: The straight leg raise (SLR) maneuver during high-resolution manometry (HRM) can assess esophagogastric junction (EGJ) barrier function by measuring changes in intraesophageal pressure (IEP) when intra-abdominal pressure is increased. We aimed to determine whether increased esophageal pressure during SLR predicts pathologic esophageal acid exposure time (AET). METHODS: Adult patients with persistent gastroesophageal reflux disease (GERD) symptoms undergoing HRM and pH-impedance or wireless pH study off proton pump inhibitor were prospectively studied between July 2021 and March 2022. After the HRM Chicago 4.0 protocol, patients were requested to elevate 1 leg at 45º for 5 seconds while supine. The SLR maneuver was considered effective when intra-abdominal pressure increased by 50%. IEPs were recorded 5 cm above the lower esophageal sphincter at baseline and during SLR. GERD was defined as AET greater than 6%. RESULTS: The SLR was effective in 295 patients (81%), 115 (39%) of whom had an AET greater than 6%. Hiatal hernia (EGJ type 2 or 3) was seen in 135 (46%) patients. Compared with patients with an AET less than 6%, peak IEP during SLR was significantly higher in the GERD group (29.7 vs 13.9 mm Hg; P < .001). Using receiver operating characteristic analysis, an increase of 11 mm Hg of peak IEP from baseline during SLR was the optimal cut-off value to predict an AET greater than 6% (area under the receiver operating characteristic curve, 0.84; sensitivity, 79%; and specificity, 85%), regardless of the presence of hiatal hernia. On multivariable analysis, an IEP pressure increase during the SLR maneuver, EGJ contractile integral, EGJ subtype 2, and EGJ subtype 3, were found to be significant predictors of AET greater than 6% CONCLUSIONS: The SLR maneuver can predict abnormal an AET, thereby increasing the diagnostic value of HRM when GERD is suspected. CLINICALTRIALS: gov ID: NCT04813029.

Minimally invasive oesophagectomy in the prone versus lateral decubitus position: a systematic review and meta-analysis.

The thoracic phase of minimally invasive esophagectomy was initially performed in the lateral decubitus position (LDP); however, many experts have gradually transitioned to a prone position (PP) approach. The aim of the present systematic review and meta-analysis is to quantitatively compare the two approaches. A systematic literature search of the MEDLINE, Embase, Google Scholar, Web of Knowledge, China National Knowledge Infrastructure and ClinicalTrials.gov databases was undertaken for studies comparing outcomes between patients undergoing minimally invasive esophageal surgery in the PP versus the LDP. In total, 15 studies with 1454 patients (PP; n = 710 vs. LDP; n = 744) were included. Minimally invasive esophagectomy in the PP provides statistically significant reduction in postoperative respiratory complications (Risk ratios 0.5, 95% confidence intervals [CI] 0.34-0.76, P < 0.001), blood loss (weighted mean differences [WMD] -108.97, 95% CI -166.35 to -51.59 mL, P < 0.001), ICU stay (WMD -0.96, 95% CI -1.7 to -0.21 days, P = 0.01) and total hospital stay (WMD -2.96, 95% CI -5.14 to -0.78 days, P = 0.008). In addition, prone positioning increases the overall yield of chest lymph node dissection (WMD 2.94, 95% CI 1.54-4.34 lymph nodes, P < 0.001). No statistically significant difference in regards to anastomotic leak rate, mortality and 5-year overall survival was encountered. Subgroup analysis revealed that the protective effect of prone positioning against pulmonary complications was more pronounced for patients undergoing single-lumen tracheal intubation. A head to head comparison of minimally invasive esophagectomy in the prone versus the LDP reveals superiority of the former method, with emphasis on the reduction of postoperative respiratory complications and reduced length of hospitalization. Long-term oncologic outcomes appear equivalent, although validation through prospective studies and randomized controlled trials is still necessary.

Eosinophilic Esophagitis and Achalasia: Two Distinct Nosologic Entities or a Possible Etiopathogenic Association?

BACKGROUND: Despite the fact that researchers have made significant progress in elucidating the pathophysiology of esophageal diseases, the understanding of esophageal motility alterations in patients with eosinophilic esophagitis (EoE) is in its infancy and current published medical literature remains rather scarce on this topic. A growing body of scientific data regarding associations between esophageal motor disorders, such as achalasia and EoE, exists nowadays. SUMMARY: It seems that the association of EoE and achalasia does not constitute a cause and effect relationship, as it is not clear whether esophageal motility abnormalities are the result of EoE or vice versa. As such, there is no universally accepted treatment algorithm for patients presenting with both of these entities. Key Messages: The aim of this article is to review the existing data on achalasia-like motility disorders in patients with EoE, highlighting a possible association between these 2 esophageal disorders. Moreover, we seek to describe the clinical presentation in such cases, diagnostic modalities to be used, and current treatment strategies in patients suspected to suffer from both disorders.

Implementation of minimally invasive gastrectomy for gastric cancer in a western tertiary referral center.

BACKGROUND: Minimally invasive techniques have gradually come to take a leading position in the surgical treatment of gastrointestinal malignancies. In order to define an effective process for the implementation of similar techniques in the treatment of gastric cancer, patient caseload represents a pivotal factor for education and training, but is a prerequisite not fulfilled in most Western countries. Additionally, as opposed to the East, a variety of additional factors such as the usually advanced stage of the disease and differences in patient characteristics are prevailing and raise further obstacles. Hereby we report a strategy for a safe and effective process for the implementation of laparoscopic gastric cancer surgery in a Western tertiary referral center. METHODS: The present study describes the stepwise implementation of laparoscopic gastrectomy for the treatment of gastric cancer at a tertiary referral center, comprising the time period 2012-2019. This process was facilitated by a close collaboration with two high-volume centers in Japan, as well as exchanging fellowships and observerships between the Karolinska University Hospital and other European centers. From the initially strict selection of cases for laparoscopic surgery, laparoscopic gastrectomy has gradually become the preferred approach also in patients with locally advanced tumors. RESULTS: From January 1st 2010 until December 31st 2019, 249 patients were operated for gastric cancer, of whom 141 (56.6%) had an open and 108 (43.4%) a laparoscopic procedure. In the latter group, total gastrectomy was performed in 33.3% of the patients. While blood loss, operation time and length of stay decreased during the first years after implementation, these variables increased slightly during the last years of the study period, probably due to the higher proportion of advanced gastric cancer cases, as well as the higher rate of laparoscopic total gastrectomy with more extended lymphadenectomy. CONCLUSIONS: Laparoscopic surgery is currently a valid therapeutic option for gastric cancer, which has expanded to also embrace total gastrectomy and locally advanced tumors. Collaboration between centers in the East and West, centralization to high-volume centers and application of enhanced recovery protocols are essential components in the implementation and further refinement of minimally invasive gastrectomy.

Enhanced recovery pathways vs standard care pathways in esophageal cancer surgery: systematic review and meta-analysis.

Enhanced recovery after surgery (ERAS) protocols vs standard care pathways after esophagectomy for malignancy have gained wide popularity among surgeons. However, the current literature is still lacking level-I evidence to show a clear superiority of one approach. The present study is a detailed systematic review and meta-analysis of the published trials. A systematic review of literature databases was conducted for randomized controlled trials (RCTs) and non-randomized, prospective, comparative studies between January 1990 and September 2019, comparing ERAS pathway group with standard care for esophageal resection for esophageal cancer. Mean difference (MD) for continuous variables and odds ratio (OR) or risk difference (RD) for dichotomous variables with 95% confidence interval (CI) were used. Between-study heterogeneity was evaluated. Eight studies with a total of 1133 patients were included. Hospital stay [Standard mean difference (Std. MD) = - 1.92, 95% CI - 2.78, - 1.06, P < 0.0001], overall morbidity (OR 0.68, CI 0.49, 0.96, P = 0.03), pulmonary complications (OR 0.45, CI 0.31, 0.65, P < 0.0001), anastomotic leak rate (OR 0.37, CI 0.18, 0.74, P = 0.005), time to first flatus and defecation (Std. MD = -5.01, CI - 9.53, - 0.49, P = 0.03), (Std. MD = - 1.36, CI - 1.78, - 0.94, P < 0.00001) and total hospital cost (Std. MD = - 1.62, CI - 2.24, - 1.01, P < 0.00001) favored the ERAS group. Patients who undergo ERAS have a clear benefit over the standard care protocol. However, existing protocols in different centers are followed by great variability, while the evaluated parameters suffer from significant heterogeneity. A well-formulated, standardized protocol should be standard-of-care at all centers.

Pseudoachalasia: a systematic review of the literature.

Pseudoachalasia, also known as secondary achalasia, is a clinical condition mimicking idiopathic achalasia but most commonly caused by malignant tumors of gastroesophageal junction (GEJ). Our aim was to systematically review and present all available data on demographics, clinical features, and diagnostic modalities involved in patients with pseudoachalasia. A systematic search of literature published during the period 1978-2019 was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (end-of-search date: June 25th, 2019). Two independent reviewers extracted data with regards of study design, interventions, participants, and outcomes. Thirty-five studies met our inclusion criteria and were selected in the present review. Overall, 140 patients with pseudoachalasia were identified, of whom 83 were males. Mean patient age was 60.13 years and the mean weight loss was 13.91 kg. A total of 33 (23.6%) patients were wrongly 'treated' at first for achalasia. The most common presenting symptoms were dysphagia, food regurgitation, and weight loss. The median time from symptoms' onset to hospital admission was 5 months. Most common etiology was gastric cancer (19%). Diagnostic modalities included manometry, barium esophagram, endoscopy, and computed tomography (CT). Pseudoachalasia is a serious medical condition that is difficult to be distinguished from primary achalasia. Clinical feature assessment along with the correct interpretation of diagnostic tests is nowadays essential steps to differentiate pseudoachalasia from idiopathic achalasia.

Current status of esophageal cancer treatment.

Esophageal cancer (EC) remains one of the most common and aggressive diseases worldwide. This review discusses some debates in the modern management of the disease. Endoscopic procedures for early cancer (T1a-b) are now embedded in routine care and the challenge will be to more accurately select patients for endoscopic resection with or without adjuvant therapy. Perioperative multimodal therapies are associated with improved survival compared to surgery alone for locally advanced esophageal cancer. However, there is no global consensus on the optimal regimen. Furthermore, histological subtype (adenocarcinomavs. squamous cell cancer) plays a role in the choice for treatment. New studies are underway to resolve some issues. The extent of the lymphadenectomy during esophagectomy remains controversial especially after neoadjuvant chemoradiation. The ideal operation balances between limiting surgical trauma and optimizing survival. Minimally invasive esophagectomy and enhanced recovery pathways are associated with decreased morbidity and faster recovery albeit there is no consensus yet what approach should be used. Finally, immune checkpoint inhibitors present promising preliminary results in the novel treatment of advanced or metastatic EC but their widespread application in clinical practice is still awaited.

Efficacy of esophageal stents as a primary therapeutic option in spontaneous esophageal perforations: a systematic review and meta-analysis of observational studies.

Background: Spontaneous esophageal perforation traditionally mandates urgent surgical treatment. Lately, esophageal stents have been used to reduce the associated morbidity and mortality. The current systematic review aimed to assess the efficacy of stents as a primary treatment option in this scenario. Methods: A systematic search was conducted in PubMed/MEDLINE, Scopus and the Cochrane Library for studies published in the English language between 2000 and 2023. We included observational studies reporting on the use of stents, alongside conservative measures and drainage procedures, in patients with spontaneous esophageal perforations. Primary outcomes were sealing rate (persistent leak occlusion) and failure rate (mortality or conversion to a major surgical operation). Secondary outcomes included patients' presentation, sepsis, drainage procedures, and reinterventions. Results for primary outcomes were presented as pooled rates with 95% confidence intervals (CIs), using a random-effects model. Methodological quality was assessed using the MINORS score. Results: Eighteen studies involving 171 patients were included. Sealing rate was 86% (95%CI 77-93%) and failure rate was 14% (95%CI 7-22%). Weighted mortality rate was 6% (95%CI 2-13%), while conversion to surgical treatment was 2% (95%CI 0-9%). Late presentation was not related to a statistically significant increase in treatment failure (odds ratio 1.85, 95%CI 0.37-9.30; P=0.72). Drainage procedures were required for the majority of patients, with a high rate of surgical and endoscopic reinterventions. Conclusions: Our results imply that stents may offer an effective and safe alternative treatment for patients with spontaneous esophageal perforations. Additional endoscopic and surgical drainage procedures are frequently needed.

The Milan score: A novel manometric tool for a more efficient diagnosis of gastro-esophageal reflux disease.

OBJECTIVE: A definitive diagnosis of gastroesophageal reflux disease (GERD) depends on endoscopic and/or pH-study criteria. However, high resolution manometry (HRM) can identify factors predicting GERD, such as ineffective esophageal motility (IEM), esophago-gastric junction contractile integral (EGJ-CI), evaluating esophagogastric junction (EGJ) type and straight leg raise (SLR) maneuver response. We aimed to build and externally validate a manometric score (Milan Score) to stratify the risk and severity of the disease in patients undergoing HRM for suspected GERD. METHODS: A population of 295 consecutive patients undergoing HRM and pH-study for persistent typical or atypical GERD symptoms was prospectively enrolled to build a model and a nomogram that provides a risk score for AET > 6%. Collected HRM data included IEM, EGJ-CI, EGJ type and SLR. A supplemental cohort of patients undergoing HRM and pH-study was also prospectively enrolled in 13 high-volume esophageal function laboratories across the world in order to validate the model. Discrimination and calibration were used to assess model's accuracy. Gastroesophageal reflux disease was defined as acid exposure time >6%. RESULTS: Out of the analyzed variables, SLR response and EGJ subtype 3 had the highest impact on the score (odd ratio 18.20 and 3.87, respectively). The external validation cohort consisted of 233 patients. In the validation model, the corrected Harrel c-index was 0.90. The model-fitting optimism adjusted calibration slope was 0.93 and the integrated calibration index was 0.07, indicating good calibration. CONCLUSIONS: A novel HRM score for GERD diagnosis has been created and validated. The MS might be a useful screening tool to stratify the risk and the severity of GERD, allowing a more comprehensive pathophysiologic assessment of the anti-reflux barrier. TRIAL REGISTRATION: ClinicalTrials.gov (Identifier: NCT05851482).

The Implementation of Minimally Invasive Surgery in the Treatment of Esophageal Cancer: A Step Toward Better Outcomes?

Esophagectomy is considered the cornerstone of the radical treatment of esophageal cancer. In the past decades, minimally invasive techniques including robot-assisted approaches have become popular. The aim of minimally invasive surgery is to reduce the surgical trauma, resulting in faster recovery, reduction in complications, and better quality of life after surgery. Secondly, a more precise dissection may lead to better oncological outcomes. As such, minimally invasive esophagectomy is now seen by many as the standard surgical approach. However, evidence supporting this viewpoint is limited. This narrative review summarizes recent prospectively designed studies on minimally invasive esophagectomy.

Implant infections after breast reconstruction surgery following mastectomy: Experience from a Greek breast unit.

BACKGROUND: Despite the dominance of implant-based breast reconstruction after mastectomy, during recent years, it has been correlated to some complications. The aim of this study is to present the Greek experience about management of implant infections after breast reconstructions and to investigate the relationship between possible risk factors and breast pocket fluid cultures. METHODS: In total, 260 patients underwent implant-based breast reconstruction due to breast cancer in our center from 2016 until 2020. 46 patients, that underwent implant or expander replacement after breast reconstruction due to mastectomy were included in the present study. RESULTS: 260 patients underwent breast reconstruction in our center and in 46 (18%) of them an implant replacement was required. 21 patients (8%) presented clinically with an implant infection, but 12 of them (5%) had positive cultures from the breast pocket fluid. On the contrary, 25 patients (10%) presented no clinical signs of implant infection, but 5 of them (2%) had a positive culture. In addition, we demonstrated a correlation between implant infection and positive cultures (p = 0.009), along with an association between chemotherapy before implant placements and negative cultures (p = 0.035). Finally, the most common pathogen was Staphylococcus epidermidis (29%), followed by Escherichia coli (24%) and Staphylococcus aureus (18%). CONCLUSION: Implant infection still remains a very serious complication after breast reconstruction surgery. The establishment of a therapeutic protocol, with specific antimicrobial and surgical targets seems as an effective strategy against implant infections.

Multidisciplinary treatment of esophageal cancer: The role of active surveillance after neoadjuvant chemoradiation.

The optimal treatment of esophageal cancer is still controversial. Neoadjuvant chemoradiotherapy followed by radical esophagectomy is a standard treatment. Morbidity after esophagectomy however is still considerable and has an impact on patients' quality of life. Given a pathologic complete response rate of approximately 30% in patients after neoadjuvant chemoradiation followed by surgery, active surveillance has been introduced as a new alternative approach. Active surveillance involves regular clinical response evaluations in patients after neoadjuvant therapy to detect residual or recurrent disease. As long as there is no suspicion of disease activity, surgery is withheld. Esophagectomy is reserved for patients presenting with an incomplete response or resectable recurrent disease. Active surveillance after neoadjuvant treatment has been previously applied in other types of malignancy with encouraging results. This paper discusses its role in esophageal cancer.

Esophageal cancer: challenges, concerns, and recommendations for management amidst the COVID-19 pandemic.

Since December 2019, the outbreak of coronavirus disease 2019 (COVID-19) has rapidly spread worldwide, raising great concern, particularly in immunosuppressed cancer patients. The pandemic situation remains extremely dynamic, which necessitates proactive management decisions from oncologists and oncologic surgeons in effort to mitigate the risk of both SARS-CoV-2 infection and cancer metastasis. Esophageal cancer, in particular, is one of the deadliest types of malignancy worldwide, reflecting both aggressive biology and a lack of adequate treatment. Several challenges and concerns regarding the management of esophageal cancer have been raised in light of the ongoing viral pandemic. The primary aim of this review is to summarize the salient evidence for recommendations and optimal treatment strategies for patients with esophageal cancer amidst the COVID-19 pandemic.

A Decade of Investigation: Peroral Endoscopic Myotomy Versus Laparoscopic Heller Myotomy for Achalasia.

Background: Although laparoscopic Heller myotomy (LHM) with partial fundoplication has long been considered the gold standard for treatment of patients with achalasia, peroral endoscopic myotomy (POEM) has emerged in the last decade as a viable alternative. Methods: A collective review of literature concerning investigations that have reported patient outcomes and treatment success of LHM and POEM for all achalasia subtypes. Results: While POEM has shown excellent short-term safety and efficacy in the relief of symptoms, the long-term symptomatic outcomes after the intervention are yet to be concluded. Further evaluation of patients' interpretations and answers on subjective questionnaires is warranted before determining treatment success for POEM. Use of more reliable and disease-specific health-related quality-of-life questionnaires are better justified when comparing a new endoscopic procedure to an established gold standard. The need for objective parameters to measure reflux, longer follow-up studies, and randomized trials comparing POEM to LHM is particularly important when assessing the outcome of this new technique. High incidence of post-POEM pathologic reflux and indication for daily proton pump inhibitor use is of concern, and the lack of more long-term, objective evidence leaves the clinical value of the procedure in a state of uncertainty. Conclusions: The LHM combined with partial fundoplication is still considered to be the gold standard treatment modality for achalasia, but as the POEM procedure rapidly becomes common practice, this treatment may be performed in the majority of achalasia cases. Given the number of flaws overlooked in seminal investigations, careful consideration should be given to the patients being selected for this therapy.

Evaluation of plasma and tissue expression levels of Endothelins (ET-1, Big ET-1) and VEGF in lobular neoplasia of the breast.

PURPOSE: The endothelin system is involved in the evolution of multiple malignancies, participating in cancer cell proliferation, tumor invasion and angiogenesis. Our purpose was to simultaneously assess endothelin expression in the systemic circulation of patients with lobular neoplasia (LN) of the breast and to investigate its correlation with vascular endothelial growth factor (VEGF) specimen expression levels as well as clinicopathologic findings. METHODS: This was a retrospective analysis of prospectively collected data regarding 60 women examined in a single breast unit. Thirty of these women underwent stereotactic biopsy and were diagnosed with LN and the remaining 30 were healthy controls. Circulating levels of endothelin (ET)-1 and Big ET-1 were measured using ELISA, while tissue expression of ET-1 and VEGF in biopsy specimens were assessed using qualitative immunohistochemical staining. RESULTS: The plasma levels of Big ET-1 were significantly increased in patients with LN compared to healthy controls. There was no significant difference in the plasma levels of ET-1 between the patient groups. In patients with LN, plasma expression of ET-1 and Big ET-1 did not correlate with ET-1 or VEGF tissue expression status, neither existed a relationship between tissue expressions of ET-1 and VEGF. CONCLUSIONS: Our results imply that Big ET-1 is a potential biomarker for LN. Further investigation of the endothelin system role in LN seems a promising research field.

Non-Recurrent Right Laryngeal Nerve: a Rare Anatomic Variation Encountered During a Total Thyroidectomy.

The non-recurrent laryngeal nerve (nRLN) is a rare anatomic variation that every head and neck surgeon must be aware of, in order to avoid intraoperative injury which leads to postoperative morbidity. We are reporting a case of a nRLN in a 47 year old female patient with medullary thyroid carcinoma who was surgically treated with total thyroidectomy and lymph node dissection. Both two inferior laryngeal nerves were identified, fully exposed and preserved along their cervical courses. However, we found that the right inferior laryngeal nerve was non-recurrent and directly arised from the cervical vagal trunk, entered the larynx after a short transverse course and parallel to the inferior thyroid artery. The safety of thyroid operations is dependent on high index of suspicion, meticulous identification and dissection of laryngeal nerves either recurrent or non-recurrent. This leads to minimum risk of iatrogenic damage of the nerves. Complete knowledge of the anatomy of these neural structures, including all their anatomic variations is of paramount importance.

Long-term outcome of myotomy and fundoplication based on intraoperative real-time high-resolution manometry in achalasia patients.

BACKGROUND: Current treatment options for achalasia of the esophagus predominantly consist of endoscopic myotomy or laparoscopic myotomy combined with a partial fundoplication. The intraoperative use of conventional manometry has previously been proposed with various results. The aim of the present study was to introduce the use of high-resolution manometry (HRM) during surgical treatment for achalasia and to assess the long-term outcome of this technique. METHODS: We enrolled achalasia patients within the time period November 2013 to July 2016 who underwent HRM and evaluation of Eckardt scores (ES) before and after tailored laparoscopic myotomy and fundoplication with intraoperative recording using HRM. RESULTS: Twenty patients were classified as having achalasia type I (20%), type II (55%), or type III (25%). During surgery, 9 myotomies were extended and 13 fundoplications were modified according to HRM findings. Mean resting (16.1 vs. 41.9 mmHg) and residual (9 vs. 28.7 mmHg) pressures of the lower esophageal sphincter and ES (0.7 vs. 6.9) were significantly eliminated postoperatively over a mean follow-up time of 17.7 months. CONCLUSIONS: The use of intraoperative HRM gives us the advantage of simultaneous real-time estimation of intraluminal pressures of the esophagus and the ability to identify the exact points that produce pressure during laparoscopy. Consequently, it may be the key to the tailoring of the Heller-Dor technique and improving the outcomes for achalasia patients.

First genotype-phenotype study reveals HLA-DQß1 insertion heterogeneity in high-resolution manometry achalasia subtypes.

Background: Achalasia is a primary oesophageal motility disorder. Although aetiology remains mainly unknown, a genetic risk variant, rs28688207 in HLA-DQB1, showed strong achalasia association suggesting involvement of immune-mediated processes in the pathogenesis. High-resolution manometry recognises three types of achalasia. The aim of our study was to perform the first genotype-phenotype analysis investigating the frequency of rs28688207 across the high-resolution manometry subtypes. Methods: This was a cross-sectional retrospective study. Achalasia patients from tertiary centres in the Czech Republic (n = 163), Germany (n = 114), Greece (n = 70) and controls were enrolled. All subjects were genotyped for the rs28688207 insertion. The Kruskal-Wallis test was used for the genotype-phenotype analysis. Results: A total of 347 achalasia patients (type I - 89, II - 210, III - 48) were included. The overall frequency of the rs28688207 was 10.3%. The distribution of the insertion was significantly different across the high-resolution manometry subtypes (p = 0.038), being most prevalent in type I (14.6%), followed by type II (9.5%) and III (6.3%). Conclusion: The frequency of the HLA-DQB1 insertion differs among high-resolution manometry achalasia subtypes. The insertion is most prevalent in type I, suggesting that immune-mediated mechanisms triggered by the insertion may play a more prominent role in the pathogenesis of this subtype.