Risk of lymph node metastasis in T1 esophageal adenocarcinoma: a meta-analysis.

Patients with early (T1) esophageal adenocarcinoma (EAC) are increasingly having definitive local therapy endoscopically. Endoscopic resection is not able to pathologically stage or treat lymph node metastasis (LNM). Accurate identification of patients having nodal metastasis is critical to select endoscopic therapy over surgery. This study aimed to define the risk of LNM in T1 EAC. A meta-analysis of studies of patients who underwent surgery and lymphadenectomy with assessment of LNM was performed according to PRISMA. Main outcome was probability of LNM in T1a and T1b disease. Secondary outcomes were risk factors for LNM and rate of LNM in submucosal T1b (SM1, SM2, and SM3) disease. Registered with PROSPERO (CRD42022341794). Twenty cohort studies involving 2264 patients with T1 EAC met inclusion criteria: T1a (857 patients) with 36 (4.2%) node positive and T1b (1407 patients) with 327 (23.2%) node positive. Subgroup analysis of T1b lesions was available in 10 studies (405 patients). Node positivity for SM1, SM2, and SM3 was 16.3%, 16.2%, and 29.4%, respectively. T1 substage (odds ratio [OR] 7.72, 95% confidence interval [CI] 4.45-13.38, P < 0.01), tumor differentiation (OR 2.82, 95% CI 2.06-3.87, P < 0.01), and lymphovascular invasion (OR 13.65, 95% CI 6.06-30.73, P < 0.01) were associated with LNM. T1a disease demonstrated a 4.2% nodal metastasis rate and T1b disease a rate of 23.2%. Endoscopic therapy should be reserved for T1a disease and perhaps select T1b disease, which has a moderately high rate of nodal metastasis. There were inadequate data to stratify T1b SM disease into 'low-risk' and 'high-risk' based on tumor differentiation and lymphovascular invasion.

Extensive lymphadenectomy may improve survival in node negative oesophageal cancer.

Lymph node metastases are a major prognostic factor in survival of patients with oesophageal cancer. The number of lymph nodes removed during oesophagectomy has been previously proven to be associated with improved survival. The aim of this study was to examine the effect of lymph node harvest on survival specifically in pathologically node negative (pN0) patients with oesophageal cancer. Data were extracted from a prospectively populated single-surgeon database of oesophageal resections for cancer. All consecutive patients with pN0 were included. Patient-specific risk adjusted analysis of overall and disease-free survival was performed to identify the number of lymph nodes associated with improved survival. Inclusion criteria were met by 137 patients (49 squamous cell carcinoma and 88 adenocarcinoma). Adjusted for cancer stage, tumour (histological type, degree of differentiation, lympho-vascular invasion, neo-adjuvant therapy) and patient related factors (age, sex), increased lymph node number was associated with significant improvement in overall (P = 0.045) and disease free (P = 0.030) survival. Lymph node count ≥ 17 was associated with improved overall and disease-free survival. In this cohort of patients with pathologically node-negative oesophageal cancer, lymph node count of 17 or above was associated with significantly improved survival.

Durability of radiofrequency ablation for long-segment and ultralong-segment Barrett's esophagus over 10 years.

BACKGROUND: Long-term durability data for radiofrequency ablation (RFA) to prevent esophageal adenocarcinoma in long-segment (LSBE) and ultralong-segment Barrett's esophagus (ULSBE) is lacking. This study aimed to determine 10-year cancer progression, eradication, and complication rates in LSBE and ULSBE patients treated with RFA. METHODS: Single-surgeon prospective database of patients with LSBE (≥ 3 to < 8 cm) and ULSBE (≥ 8 cm) who underwent RFA (2001-2021) were retrospectively analyzed. Ten-year cancer progression calculated with Kaplan-Meier analysis. Eradication rates, including complete remission of dysplasia (CR-D) and intestinal metaplasia (CR-IM), and rates of recurrence and complications, compared between LSBE and ULSBE groups. RESULTS: Ten years after starting treatment, the cancer rate was 14.3% in 56 patients. CR-D and CR-IM rates were 87.5% and 67.9%, respectively. Relapse rates from CR-D were 1.8% and 3.6% from CR-IM. Eradication rates for dysplasia in LSBE and ULSBE patients (90.6% versus 83.3%) and IM (71.9% versus 62.5%) were not significantly different. ULSBE patients required higher mean number of ablation sessions for IM eradication (4.7 versus 3.7, p = 0.032), while complication rates including strictures (4.2% versus 6.2%), perforation (0 versus 0), and bleeding (4.2% versus 3.1%), were similar between ULSBE and LSBE patients, respectively. On multivariate analysis, shorter Barrett's segment and baseline low-grade dysplasia were associated with increased likelihood for eradication of IM and dysplasia. A total number of ablation sessions or endoscopic resections ≥ 3 was associated with reduced likelihood for eradication. CONCLUSION: RFA was durable in maintaining dysplasia and IM eradication in both LSBE and ULSBE over 10 years, and with low complication rates. IM eradication was more difficult to achieve in ULSBE. Late development of cancer occurred in 14.3%.

Laparoscopic common bile duct exploration: what factors determine success?

BACKGROUNDS: Laparoscopic common bile duct exploration (LCBDE) has been shown to be effective in managing choledocholithiasis whilst avoiding ERCP-related complications. However, patient and technical factors effects outcome. This study aimed to explore the matters effecting the failure of LCBDE. METHODS: All patients who underwent a laparoscopic cholecystectomy (LC) between 2007 and 2021 were identified using a prospective database. Data were collected for patients who underwent LCBDE including demographics, pre-operative investigations, intra-operative findings, technique of bile duct clearance and clearance rates, and post-operative outcomes. Predictors of failed LCBDE were identified. RESULTS: Laparoscopic cholecystectomy was performed in 3648 patients. Of these, 374 underwent LCBDE for suspected choledocholithiasis. Choledochoscopy was most frequently used (58.8%) with a success rate of 84.1%. Small cystic duct diameter (4.7 vs. 3.4 mm, P = 0.002), stone size >6 mm (P = 0.02), stone: cystic duct ratio >1 (P = 0.04), and >3 stones was associated with failed LCBDE by univariate analysis. Small cystic duct diameter (OR: 0.45, 95% CI: 0.26-0.77, P = 0.004) and stone size >6 mm (OR: 0.23, 95% CI: 0.06-0.92), P = 0.04) correlated with failure by multivariate analysis. Failed LCBDE was associated with increased length of stay (6.6 days vs. 3.1 days, P = 0.001), however the rate of serious complications or mortality was unaffected. CONCLUSION: LCBDE is safe and effective in managing choledocholithiasis. Factors such as cystic duct diameter, size and number of CBD stones, and stone: cystic duct ratio are associated with increased likelihood of inadequate clearance. The presence of these factors can help clinicians in decision making during LCBDE to improve chance of success.

Recurrence in Paraesophageal Hernia: Patient Factors and Composite Surgical Repair in 862 Cases.

BACKGROUND: Repair of giant paraesophageal hernia (PEH) is associated with a considerable hernia recurrence rate by objective measures. This study analyzed a large series of laparoscopic giant PEH repair to determine factors associated with anatomical recurrence. METHOD: Data was extracted from a single-surgeon prospective database of laparoscopic repair of giant PEH from 1991 to 2021. Upper endoscopy was performed within 12 months postoperatively and selectively thereafter. Any supra-diaphragmatic stomach was defined as anatomical recurrence. Patient and hernia characteristics and technical operative factors, including "composite repair" (360° fundoplication with esophagopexy and cardiopexy to right crus), were evaluated with univariate and multivariate analysis. RESULTS: Laparoscopic primary repair was performed in 862 patients. The anatomical recurrence rate was 27.3% with median follow-up of 33 months (IQR 16, 68). Recurrence was symptomatic in 45% of cases and 29% of these underwent a revision operation. Hernia recurrence was associated with younger age, adversely affected quality of life, and were associated with non-composite repair. Multivariate analysis identified age < 70 years, presence of Barrett's esophagus, absence of "composite repair", and hiatus closure under tension as independent factors associated with recurrence (HR 1.27, 95%CI 0.88-1.82, p = 0.01; HR 1.58, 95%CI 1.12-2.23, p = 0.009; HR 1.72, 95%CI 1.2-2.44, p = 0.002; HR 2.05, 95%CI 1.33-3.17, p = 0.001, respectively). CONCLUSION: Repair of giant PEH is associated with substantial anatomical recurrence associated with patient and technique factors. Patient factors included age < 70 years, Barrett's esophagus, and hiatus tension. "Composite repair" was associated with lower recurrence rate.

A putative link between pertussis and new onset of gastroesophageal reflux an observational study.

Background: Pertussis is an infectious disease of the respiratory tract with a changing epidemiology. An increasing incidence has been found in the adult population with recurrent infections possibly related to changes in the current vaccine. Is there an association between pertussis infection, refractory cough and atypical gastro-oesophageal reflux (GORD)? Does this magnify and compound respiratory complications? Methods: Observational study which compares post-pertussis (n=103) with non-pertussis patients (n=105) with established GORD. Patients were assessed for laryngopharyngeal reflux and aspiration of refluxate by a novel scintigraphic study. Results: Both groups showed severe GORD in association with high rates of laryngopharyngeal reflux (LPR) and pulmonary aspiration and lung disease. High rates of hiatus hernia and clinical diagnosis of "atypical" asthma showed correlations with pulmonary aspiration. Conclusions: A high level of new onset LPR and lung aspiration has been shown in patients with chronic cough after recent pertussis infection by a novel scintigraphic technique with fused hybrid x-ray computed tomography (SPECT/CT).

Acute oxygen desaturation characterizes pulmonary aspiration in patients with gastroesophageal reflux disease and laryngopharyngeal reflux.

The aim of this study was to characterise pulmonary aspiration of refluxate in patients with gastroesophageal reflux disease (GORD) and laryngopharyngeal reflux (LPR) by continuous pulse oximetry (SpO2) during the supine phase of a scintigraphic reflux study. Variables assessed for significance included age, hiatus hernia, frequency, amplitude of reflux and clearance of reflux from the oesophagus/pharynx. The patients included in this study had established GORD and LPR by clinical history. All patients underwent fused three- dimensional scintigraphic/ X-ray computed tomography (CT) and simultaneous continuous pulse oximetry when supine for 30 minutes. A total of 265 patients (40.4% M, 59.6% F) were studied. Mean age of aspirators was 57.0 years and non-aspirators was 53.5 years. Seven patients had baseline oxygen saturation <95%, with 6/7 showing aspiration by scintigraphy. The remainder had mean baseline saturation of 97.7%. Continuous SpO2 monitoring showed a significant fall in pulmonary aspirators after 20 min of supine acquisition with significant variability. Analysis revealed a cyclic event every 1.5 min in aspirators only. Panel regression analysis showed a significant effect of age, hiatus hernia, pulse rate and reflux frequency on the fall in SpO2. Pulmonary aspiration in patients with LPR and GORD is characterised by acute oxygen desaturation. Variables affecting oxygen desaturation were age, hiatus hernia, pulse rate and reflux frequency. A cyclic event was observed every 1.5 min in aspirators and may be due to reflex homeostatic mechanism attempting to correct perceived hypoxia.

Failed fundoplication with delayed gastric emptying: efficacy of subtotal gastrectomy.

BACKGROUND: The management of patients with gastroparesis and recurrent reflux after previous fundoplication is challenging. The aim of this study was to evaluate the safety and efficacy of subtotal gastrectomy with Roux-en-Y reconstruction as a remedial procedure in this select patient population. METHOD: Retrospective analysis of a prospectively populated database identified all patients that underwent subtotal gastrectomy with Roux-en-Y reconstruction (SGRNY) due to reflux symptoms and delayed gastric emptying (DGE). Demographic, intra-operative and post-operative data including pre and post-operative modified reflux aspiration scintigraphy studies were evaluated. Standardized questionnaires were used to assess symptomatic outcomes. RESULTS: From 2018 SGRNY has been selectively performed in 13 patients. Preoperative workup confirmed DGE and severe symptomatic reflux in all patients. The median number of previous fundoplication and or hiatal hernia operations was two (range 1-3). The mean hospital length of stay was 10 ± 6 days. Post-operative morbidity was experienced in three patients (23%). Seven patients (64%) had significant improvement or complete resolution of reflux on post-operative scintigraphy. Symptom improvement was reported in 92% of patients. CONCLUSION: In a select patient cohort with post-fundoplication reflux and DGE symptoms, SGRNY is a moderately safe and effective salvage option.

Different clinical symptom patterns in patients with reflux micro-aspiration.

BACKGROUND: Pulmonary manifestation of gastro-oesophageal reflux disease (GORD) is a well-recognised entity; however, little primary reported data exists on presenting symptoms of patients in whom reflux micro-aspiration is confirmed. The aim of this study is to report symptoms and presenting patterns of a large group of patients with confirmed reflux micro-aspiration. PATIENTS AND METHODS: Data was extracted from a prospectively populated database of patients referred to a tertiary specialist centre with severe, refractory or atypical reflux. Patients with reflux micro-aspiration on scintigraphy were included in this study. A separate group included patients with evidence of proximal reflux to the level of pharynx when supine and/or upright. RESULTS: Inclusion criteria were met by 243 patients with confirmed reflux micro-aspiration (33% males; mean age 59). Most common symptoms amongst patients with micro-aspiration were regurgitation (72%), cough (67%), heartburn (66%), throat clearing (65%) and dysphonia (53%). The most common two-symptom combinations were heartburn/regurgitation, cough/throat clearing, regurgitation/throat clearing, cough/regurgitation and dysphonia/throat clearing. The most common three-symptom combinations were cough/heartburn/regurgitation, cough/regurgitation/throat clearing and dysphonia/regurgitation/throat clearing. Cluster analysis demonstrated two main symptom groupings, one suggestive of proximal volume reflux symptoms and the other with motility/inflammatory bowel syndrome-like symptoms (bloat, constipation). CONCLUSION: The combination of typical symptoms of GORD such as heartburn or regurgitation and a respiratory or upper aero-digestive complaint such as cough, throat clearing or voice change should prompt consideration of reflux micro-aspiration.

The burden of gastroesophageal reflux disease on the cost of managing chronic diseases in Australia. The need for a new diagnostic and management paradigm.

INTRODUCTION: Chronic disease poses a major problem for the Australian healthcare system as the leading cost-burden and cause of death. Gastroesophageal reflux disease (GORD) typifies the problems with a growing prevalence and cost. We hypothesise that a scintigraphic test could optimise the diagnosis, especially in problematic extraoesophageal disease. MATERIALS AND METHODS: Data was collected from 2 groups of patients. Patients undergoing fundoplication for severe GORD (n = 30) and those with atypical symptoms (n = 30) were studied by scintigraphy and 24-hour oesophageal pH, impedance and manometry. RESULTS: Mean age of cohort was 55.8 years with 40 females and 20 males. Body mass index was a mean of 28.3. DeMeester score was normal in 12/60 with atypical symptoms and abnormal in the rest. Good correlation was shown between scintigraphy and impedance, manometry and distal pH readings. Pulmonary aspiration was shown in 25/60 (15 with atypical symptoms) and LPR in 20/30. Several impedance, manometric and scintigraphic finding were good predictors of lung aspiration of refluxate. CONCLUSION: Scintigraphy provides a good tool for screening patients with typical and atypical symptoms of GORD. It is well correlated with the standard methods for the diagnosis and provides visual evidence of LPR and lung aspiration.

Post-reflux swallow-induced peristaltic wave is impaired in laryngopharyngeal and gastro-oesophageal reflux disease.

INTRODUCTION: Laryngopharyngeal reflux (LPR) and gastro-oesophageal reflux disease (GORD) result from the reflux of gastric contents. The post-reflux swallow-induced peristaltic wave (PSPW) is an oesophageal reflex that facilitates chemical clearance of gastric contents following reflux events. PSPW index is a novel parameter that has been validated in assessing the effectiveness of chemical clearance in GORD, but not in LPR. This study aimed to assess chemical clearance in LPR and GORD by measuring PSPW indices in a consecutive series of patients. METHODS: Reviewers blindly analysed off-therapy impedance-pH tracings from 187 patients clinically categorized as LPR (n = 105) or GORD (n = 82) by predominant symptom profile. Conventional impedance-pH measures and PSPW indices were analysed. RESULTS: Mean PSPW index in the LPR group was higher than in the GORD group (39.7% (±17.7%) vs. 20.6% (±13.4%); p < 0.001). Abnormally low PSPW index (<61%) was seen in 85 (81%) of the LPR group, and 80 (97.6%) of the GORD group (p < 0.001). Area under the ROC curve for PSPW index to diagnose LPR was 0.83 (95% CI: 0.767-0.889; p < 0.001). CONCLUSION: Post-reflux swallow-induced peristaltic wave was impaired in patients with LPR as well as oesophageal GORD, indicating an abnormality of chemical clearance following a reflux episode in both groups. PSPW index was more severely impaired in gastro-oesophageal reflux disease (GORD). The present study shows PSPW index is useful in the diagnosis of both LPR and GORD and exposes an abnormality of clearance of the oesophagus.

Oesophageal adenocarcinoma: In the era of extended lymphadenectomy, is the value of neoadjuvant therapy being attenuated?

BACKGROUND: Neoadjuvant chemotherapy (NACT) and oesophagectomy is the standard of care for resectable oesophageal adenocarcinomas. Survival outcomes following resection have been improving over time while NACT remain largely unchanged. Indeed, a recent meta-analysis of randomized control trials did not demonstrate a survival benefit in adding NACT, raising the possibility that improved surgical techniques may be reducing the perceived effectiveness of NACT. AIM: To compare the effect of addition of NACT to a standardized surgery and lymphadenectomy on overall and disease-free survival in patients undergoing curative oesophagectomy for oesophageal adenocarcinoma. METHODS: Patient data were analysed from a prospectively maintained surgical survival database. Demographic, surgical, and survival outcomes were compared between groups according to treatment and nodal count. RESULTS: The data of 243 consecutive patients were identified. 79 patients were given NACT and 162 had surgery only. The NACT group were younger, and there was less frequent stage I adenocarcinoma. Overall survival was similar between NACT and surgery only groups (5YS: 48.7% vs 42.5%; P = 0.113), as was disease-free survival (5YS: 40.6% vs 39.9%; P = 0.635). There were ≥ 30 nodes removed in 46 patients, and < 30 in 197 patients, but were otherwise similar. There was improved survival in patients with ≥ 30 nodes removed than those with < 30 nodes (5YS: 64.4% vs 40.7%; P = 0.015), and a better disease-free survival that neared significance (5YS: 54.9% vs 36.6%; P = 0.078). CONCLUSION: NACT did not appear to affect overall or disease-free survival. However, an overall survival benefit was observed in patients with ≥ 30 lymph nodes removed, and a benefit in disease-free survival which was not significant.

Does age affect oesophagectomy survival: a cohort study.

BACKGROUND: Curative oesophagectomy for oesophageal cancer is associated with considerable potential mortality. Surgeons are increasingly treating older patients presenting with oesophageal cancer as the population ages. The question remains as to the survival in an older population group, many of whom are not fit for combined multimodal therapy. This study aimed to assess the effect of age on overall survival and disease-free survival in patients undergoing curative oesophagectomy for cancer. METHODS: Patient data were analysed from a prospectively maintained database. Demographic, surgical and survival outcomes were compared between groups according to age less than 75 years or 75 and older. RESULTS: Oesophagectomy was performed in 351 patients between 1990 and 2019 (283 patients <75 years, 68 patients ≥75 years). There was a higher rate of neoadjuvant chemotherapy in the younger group (37.7% versus 7.4%; P < 0.001). The 30-day mortality between younger and older groups was similar (2.5% and 2.9%; P = 0.827). There was no statistical difference in 5-year survival rates (50.3% versus 38.6%; P = 0.082) or median survival (22.6 versus 19.3 months; P = 0.053) between groups. There was no statistical difference in 5-year disease-free survival (45.1% and 35.7%; P = 0.180). CONCLUSION: Overall survival, disease-free survival and 30-day mortality rates in patients aged 75 years and older were not statistically different to their younger counterparts. On the basis of these results, older patients should not be precluded from consideration of potentially curative oesophagectomy on age alone, providing surgery may be performed at reasonable risk.

A transformational change in scintigraphic gastroesophageal reflux studies: A comparison with historic techniques.

BACKGROUND: The inclusion of scintigraphy in the diagnostic algorithm for gastroesophageal reflux is controversial due to variability in methodology and reporting. A novel scintigraphic reflux study has been developed and validated against the current standards for the diagnosis of gastroesophageal reflux disease (GORD). OBJECTIVE: To compare a new scintigraphic reflux test against historic techniques and standardised diagnostic reference tests for gastroesophageal reflux disease. METHODS: Paired scintigraphic studies were conducted in seventeen patients. All patients underwent at least one other standardised diagnostic reflux test such as 24- hour oesophageal impedance/ pH, and oesophageal manometry, barium swallow, gastroscopy or the Peptest. Patients inadvertently presented at sites B for scintigraphic reflux testing rather than at Site A which was part of an approved study. The findings from sites B did not correlate with clinical symptoms and other diagnostic reference tests from GORD. These studies were then repeated at Site A with approval from the patients. A second reflux study was performed at site A, utilising a novel technique with the capability of assessing oesophageal and extra-oesophageal disease. RESULTS: The Site A technique shows good concordance with the reference diagnostic tests with an accuracy of 82.4% and kappa of 0.64 (SE: 0.16, p = 0.00). Site B had an overall accuracy of 47.1% and kappa of 0.066 (SE: 0.068, p = 0.45). CONCLUSION: The Site A technique shows higher accuracy than either site B or the historic reflux techniques. It has characteristics that make it an effective screening tool for assessment of local oesophageal disease and its extraoesophageal manifestations.

Esophageal Clearance in Laryngopharyngeal Reflux Disease: Correlation of Reflux Scintigraphy and 24-hour Impedance/pH in a Cohort of Refractory Symptomatic Patients

Objectives: The role of gastroesophageal reflux disease (GERD) in the aetiology of laryngopharyngeal reflux (LPR) is poorly understood and remains a controversial issue. The 24-hour impedance monitoring has shown promise in the evaluation of LPR but is problematic in pharyngeal recording. We have shown the utility of scintigraphic studies in the detection of LPR and lung aspiration of refluxate. Correlative studies were obtained in patients with a strong history of LPR and severe GERD. Methods: A highly selected sequential cohort of patients with a high pre-test probability of LPR/severe GERD who had failed maximal medical therapy were evaluated with 24-hour impedance/pH, manometry and scintigraphic reflux studies. Results: The study group comprised 34 patients (15 M, 19 F) with a mean age of 56 years (range: 28-80 years). The majority had LPR symptoms (mainly cough) in 31 and severe GERD in 3. Impedance bolus clearance and pH studies were abnormal in all patients in the upright and supine position. A high rate of non-acid GERD was detected by impedance monitoring. LOS tone and ineffective oesophageal clearance were found in the majority of patients. Scintigraphic studies showed strong correlations with impedance, pH and manometric abnormalities, with 10 patients showing pulmonary aspiration. Conclusion: Scintigraphic studies appear to be a good screening test for LPR and pulmonary aspiration as there is direct visualisation of tracer at these sites. Impedance studies highlight the importance of non-acidic reflux and bolus clearance in the causation of cough and may allow the development of a risk profile for pulmonary aspiration of refluxate.