Timing to Surgery and Lymph Node Upstaging in Gastric Cancer: An NCDB Analysis.

BACKGROUND: Prior studies have shown tumor specificity on the impact of longer time interval from diagnosis to surgery, however in gastric cancer (GC) this remains unclear. We aimed to determine if a longer time interval from diagnosis to surgery had an impact on lymph node (LN) upstaging and overall survival (OS) outcomes among patients with clinically node negative (cN0) GC. PATIENTS AND METHODS: Patients diagnosed with cN0 GC undergoing surgery between 2004-2018 were identified in the National Cancer Database (NCDB) and divided into intervals between time of diagnosis and surgery [short interval (SI): ≥ 4 days to < 8 weeks and long interval (LI): ≥ 8 weeks]. Multivariable regression analysis evaluated the independent impact of surgical timing on LN upstaging and a Cox proportional hazards analysis and Kaplan-Meier curves evaluated survival outcomes. RESULTS: Of 1824 patients with cN0 GC, 71.8% had a SI to surgery and 28.1% had a LI to surgery. LN upstaging was seen more often in the SI group when compared to LI group (82% versus 76%, p = 0.004). LI to surgery showed to be an independent factor protective against LN upstaging [adjusted odds ratio = 0.62, 95% CI: (0.39-0.99)]. Multivariate Cox regression analysis indicated that time to surgery was not associated with a difference in overall survival [hazard ratio (HR) = 0.91, 95% CI: (0.71-1.17)], however uncontrolled Kaplan-Meier curves showed OS difference between the SI and LI to surgery groups (p = 0.037). CONCLUSION: Timing to surgery was not a predictor of LN upstaging or overall survival, suggesting that additional medical optimization in preparation for surgery and careful preoperative staging may be appropriate in patients with node negative early stage GC without affecting outcomes.

Determination of causes of post-operative dysphagia after anti-reflux surgery based on intra-operative planimetry.

INTRODUCTION: Dysphagia after anti-reflux surgery (ARS) is one of the most common indications for re-operative anti-reflux surgery and a leading cause of patient dissatisfaction. Unfortunately, the factors affecting its development are poorly understood. We investigated the correlation between pre-operative manometric and the intra-operative impedance planimetry (EndoFLIP™) measurements and development of post-operative dysphagia. METHODS: A review of patients who underwent index robotic ARS in our institution. Patients who underwent pre-operative manometry and intra-operative EndoFLIP™ were included in our study. Dysphagia was assessed pre-operatively and at 3-month after surgery. RESULTS: Fifty-five patients (26.9%) reported post-operative dysphagia, and 34 (16.6%) reported new or worsening dysphagia. On pre-operative manometry, patients with post-operative dysphagia had a lower distal contractile integral [868.7 (IQR 402.2-1447) mmHg s cm vs 1207 (IQR 612.1-2111) mmHg s cm, p = 0.006) and lower esophageal sphincter (LES) pressure [14.7 IQR (8.9-23.6) mmHg vs 20.7 IQR (10.2-32.6) mmHg, p = 0.01] compared to those without post-operative dysphagia. They were also found to have higher pre-operative cross-sectional surface area (CSA) [83 IQR (44.5-112) mm2 vs 66 IQR (42-93) mm2, p = 0.02], and distensibility index (DI) [4.2 IQR (2.2-5.5) mm2/mmHg vs 2.9 IQR (1.6-4.6) mm2/mmHg, p = 0.003] compared to patients without post-operative dysphagia. Additionally, the decrease in CSA [- 34 (- 18.5, - 74.5) mm2 vs - 26.5 (- 10.5, - 53.7) mm2, p = 0.03] and DI [- 2.3 (- 1.2, - 3.7) mm2/mmHg vs - 1.6 (- 0.7, - 3.3) mm2/mmHg, p = 0.03] measurements were greater in patients with post-operative dysphagia. CONCLUSION: Patients who developed dysphagia post-operatively had poorer pre-operative motility and a greater change in LES characteristics intra-operatively. This finding suggests the utility of pre-operative manometry and intra-operative EndoFLIP in identifying patients at risk of developing dysphagia post-operatively.

Clinical outcomes of endoscopic balloon dilation for dysphagia after anti-gastroesophageal reflux surgery.

BACKGROUND: Dysphagia is a potential complication following anti-gastroesophageal reflux surgery (ARS), with challenging management. Endoscopic balloon dilation is recommended for patients with significant dysphagia from tight wraps or strictures. We aim to evaluate factors associated with the need for post-ARS dilation and the outcomes of balloon dilation. Additionally, we assessed the predictors of sustained clinical failure after dilation. METHODS: A retrospective analysis was conducted on patients who underwent robotic or laparoscopic ARS between January 2012 and April 2023. Patients were divided based on whether they received balloon dilation using a through-the-scope wire-guided dilator. Excluded were those with pre-existing achalasia, other dilation devices, or inadequate follow-up. RESULTS: Of 1002 patients, 69 underwent 94 postoperative dilations, and the remainder were controls. The dilation cohort was older (63.78 vs. 56.14 years, P = 0.032) and had more magnetic sphincter augmentations (MSA) (P = 0.004), a prior history of ARS (P = 0.039), and a higher rate of laparoscopic surgery (P = 0.009) compared to controls. Of all dilations, 54 (57.5%) patients reported immediate dysphagia improvement, and 39 (41.5%) had sustained improvement. Sixteen (23.2%) patients required reoperation, primarily for hiatal hernia recurrence or slipped wrap. Multivariable logistic regression showed that MSA (OR 0.04, 95% CI 0.01-0.46, P = 0.031) and requiring multiple dilations (OR 0.16, CI 0.03-0.68) predicted sustained dilation failure. CONCLUSIONS: Factors including older age, history of prior ARS, and MSA are correlated with higher post-ARS dilation rates. Although dilation improves symptoms in approximately half of patients initially, one-fourth may eventually require reoperation, mostly due to a slipped wrap or hernia recurrence. Thus, in cases of persistent dysphagia, consideration for surgical failure is important, and further imaging and workup are warranted. Patients who undergo MSA and those who have more than one dilation are more likely to experience dilation failure.

The impact of obesity on gastroesophageal reflux disease recurrence following re-operative anti-reflux surgery.

INTRODUCTION: Obese patients represent a large proportion of patients experiencing recurrent reflux and re-operations after initial anti-reflux surgery. However, there is a limited data describing the impact of obesity on GERD recurrence following re-operative procedures. METHODS: A review of patients who underwent re-operative anti-reflux surgery (Re-ARS) between 2012 and 2023. Peri-operative characteristics and post-operative Gastroesophageal Reflux Disease-Health Related Quality of Life (GERD-HRQL) scores were compared across the three BMI categories: (BMI < 25 kg/m2, 25 ≤ BMI > 30 kg/m2, and BMI ≥ 30 kg/m2) over 12 IQR (9-14.9) months follow-up. Impedance planimetry measurements were included when it was utilized intraoperatively. RESULTS: Of 718 patients who underwent robotic ARS, 84 patients (11.6%) underwent Re-ARS, of which 29.7% had a BMI < 25 kg/m2, 35.7% were ≤ 25 BMI < 30 kg/m2, and 34.5% had a BMI ≥ 30 kg/m2. The lower esophageal sphincter distensibility decreased similarly between groups with no differences in post-induction [3.2 ± 2 vs 4.5 ± 3.1 vs 3.9 ± 2.5 mm2/mmHg, p = 0.44] or post-fundoplication values [1 ± 0.6 vs 1.3 ± 0.7 vs 1.2 ± 0.6 mm2/mmHg, p = 0.46]. There was a significant improvement in GERD-HRQL scores postoperatively compared to preoperative levels across the three BMI classes (BMI < 25 kg/m2: pre 17 IQR (12-22), post 7.5 (1.5-15), p = 0.04 vs ≤ 25 BMI < 30 kg/m2: pre 26 IQR (10-34), post 8 IQR (0-17), p < 0.01 vs BMI ≥ 30 kg/m2: pre 44 IQR (26-51), post 5 IQR (3.5-14.5), p < 0.001) during 12 IQR (9-14.9) months follow-up. The rates of hiatal hernia recurrence on barium swallow [5.2 vs 15.7 vs 13.7%, p = 0.32] during 7 IQR (5.2-9.2) months follow-up, and endoscopy [13.3 vs 16.6 vs 7.1%, p = 0.74] during 11.8 (IQR 5.6-17.1) months follow-up period were also similar between groups. CONCLUSION: GERD-HRQL scores in obese patients are expected to improve similarly compared to non-obese patients. Indicating that Re-ARS may be appropriate for patients across a range of BMIs.

Impedance planimetry (EndoFLIPTM) and surgical outcomes after Hill compared to Toupet fundoplication.

INTRODUCTION: Endoluminal functional lumen imaging probe (EndoFLIP) provides a real-time assessment of gastroesophageal junction (GEJ) compliance during fundoplication. Given the limited data on EndoFLIP measurements during the Hill procedure, we investigated the impact of the Hill procedure on GEJ compliance compared to Toupet fundoplication. METHODS: Patients who underwent robotic Hill or Toupet fundoplication with intraoperative EndoFLIP between 2017 and 2022 were included. EndoFLIP measurements of the GEJ included cross sectional surface area (CSA), intra-balloon pressure, high pressure zone length (HPZ), distensibility index (DI), and compliance. Subjective reflux symptoms, gastroesophageal reflux disease-health related quality of life (GERD-HRQL) score, and dysphagia score were assessed pre-operatively as well as at short- and longer-term follow-up. RESULTS: One-hundred and fifty-four patients (71.9%) had a Toupet fundoplication while sixty (28%) patients underwent the Hill procedure. The CSA [27.7 ± 10.9 mm2 vs 42.2 ± 17.8 mm2, p < 0.0001], pressure [29.5 ± 6.2 mmHg vs 33.9 ± 8.5 mmHg, p = 0.0009], DI [0.9 ± 0.4 mm2/mmHg vs 1.3 ± 0.6 mm2/mmHg, p = 0.001], and compliance [25.9 ± 12.8 mm3/mmHg vs 35.4 ± 13.4 mm3/mmHg, p = 0.01] were lower after the Hill procedure compared to Toupet. However, there was no difference in post-fundoplication HPZ between procedures [Hill: 2.9 ± 0.4 cm, Toupet: 3.1 ± 0.6 cm, p = 0.15]. Follow-up showed no significant differences in GERD-HRQL scores, overall dysphagia scores or atypical symptoms between groups (p > 0.05). CONCLUSION: The Hill procedure is as effective to the Toupet fundoplication in surgically treating gastroesophageal reflux disease (GERD) despite the lower CSA, DI, and compliance after the Hill procedure. Both procedures led to DI < 2 mm2/mmHg with no significant differences in dysphagia reporting (12-24) months after the procedure. Further studies to elucidate a cutoff value for DI for postoperative dysphagia development are still warranted.

Safety and efficacy of robotic anti-reflux surgery in geriatric patients: a comparative analysis.

INTRODUCTION: As our population ages, older adults are being considered for anti-reflux surgery (ARS). Geriatric patients typically have heightened surgical risk, and literature has shown mixed results regarding postoperative outcomes. We sought to evaluate the safety and efficacy of robotic ARS in the geriatric population. METHODS: We conducted a single-institution review of ARS procedures performed between 2009 and 2023. Patients ≥ 65 were assigned to the geriatric cohort. We compared operative details, lengths of stay (LOS), readmissions, reoperations, and complications between the two cohorts. The gastroesophageal reflux disease health-related quality of life (GERD-HRQL) survey and review of clinic notes were used to evaluate ARS efficacy. RESULTS: 628 patients were included, with 190 in the geriatric cohort. This cohort had a higher frequency of diabetes (16.3% vs 5.9% p < 0.0001), hypertension (50.0% vs 21.5% p < 0.0001), and heart disease (17.9% vs 2.3% p < 0.0001). Geriatric patients were more likely to exhibit hiatal hernias on imaging (51.6% vs 34.2% p < 0.0001) and were more likely to have large hernias (30.0% vs 7.1% p < 0.0001). Older adults were more likely to undergo Toupet fundoplications (58.4% vs 41.3%, p < 0.0001), Collis gastroplasties (9.5% vs 2.7% p < 0.0001), and relaxing incisions (11.6% vs 1.4% p < 0.0001). Operative time was longer for geriatric patients (132.0 min vs 104.5 min p < 0.0001). There were no significant differences in LOS, readmissions, or reoperations between cohorts. Geriatric patients exhibited lower rates of complications (7.4% vs. 14.6%, p = 0.011), but similar complication grades. Both groups had significant reduction in symptom scores from preoperative values. There were no significant differences in the reported symptoms between cohorts at any follow-up timepoint. CONCLUSION: Geriatric robotic ARS patients tend to do as well as younger adults regarding postoperative and symptomatic outcomes, despite presenting with larger hiatal hernias and shorter esophagi. Clinicians should be aware of possible need for lengthening procedures or relaxing incisions in this population.

Comparative anatomic and symptomatic recurrence outcomes of diaphragmatic suture cruroplasty versus biosynthetic mesh reinforcement in robotic hiatal and paraesophageal hernia repair.

BACKGROUND: Hiatal and paraesophageal hernia (HH/PEH) recurrence is the most common cause of failure after gastroesophageal anti-reflux surgery. Crural reinforcement with mesh has been suggested to address this issue, but its efficacy remains debated. In this study, we aimed to determine the impact of biosynthetic mesh reinforcement compared to suture cruroplasty on anatomic and symptomatic hernia recurrence. METHOD: Data of patients who underwent robotic HH/PEH repair with suture cruroplasty with or without biosynthetic mesh reinforcement between January 2012 and April 2024 were retrospectively reviewed. Gastroesophageal reflux disease symptoms and anatomic hernia recurrence were assessed at short-term (3 months to 1 year) and longer-term (≥ 1 year) follow-up. Symptomatic hernia recurrence was defined as having both anatomic recurrence and symptoms. RESULTS: Out of the 503 patients in the study, 308 had undergone biosynthetic mesh repair, while 195 had suture-only repair. After the surgery, both groups demonstrated comparable improvements in symptoms. Short-term anatomic hernia recurrence rates were 11.8% and 15.6% for mesh and suture groups, respectively (p = 0.609), while longer-term rates were 24.7% and 44.9% (p = 0.015). The rates of symptomatic hernia recurrence in the same group were 8.8% and 14.6% in the short-term (p = 0.256), and 17.2% and 42.2% in longer-term follow-ups (p = 0.003). In the repair of medium and large-size hernias, mesh reinforcement resulted in a 50.0% relative risk reduction in anatomic hernia recurrences and a 59.2% reduction in symptomatic hernia recurrences at ≥ 1-year follow-up. CONCLUSION: After more than a year of follow-up, it has been found that using biosynthetic mesh for medium and large hiatal or paraesophageal hernia repair significantly reduces the likelihood of both anatomic and symptomatic recurrence compared to using only suture cruroplasty. These findings strongly support the use of biosynthetic mesh to manage larger hernias. However, further long-term multicenter randomized studies are needed to provide more conclusive evidence.

Gastric development of pancreatic acinar cell metaplasia after Vonoprazan therapy in rats.

BACKGROUND: Vonoprazan is a new acid-suppressing drug that received FDA approval in 2022. It reversibly inhibits gastric acid secretion by competing with the potassium ions on the luminal surface of the parietal cells (potassium-competitive acid blockers or P-CABs). Vonoprazan has been on the market for a short time and there are many clinical trials to support its clinical application. However, medical experience and comprehensive clinical data is still limited, especially on how and if, gastric histology is altered due to therapy. METHODS: A 12-week experiment trial with 30 Wistar rats was to assess the presence of gastrointestinal morphologic abnormalities upon administration of omeprazole and vonoprazan. At six weeks of age, rats were randomly assigned to one of 5 groups: (1) saline as negative control group, (2) oral omeprazole (40 mg/kg), as positive control group, (3) oral omeprazole (40 mg/kg) for 4 weeks, proceeded by 8 weeks off omeprazole, (4) oral vonoprazan (4 mg/kg), as positive control group, and (5) oral vonoprazan (4 mg/kg) for 4 weeks, proceeded by 8 weeks off vonoprazan. RESULTS: We identified non-inflammatory alterations characterized by parietal (oxyntic) cell loss and chief (zymogen) cell hyperplasia and replacement by pancreatic acinar cell metaplasia (PACM). No significant abnormalities were identified in any other tissues in the hepatobiliary and gastrointestinal tracts. CONCLUSION: PACM has been reported in gastric mucosa, at the esophagogastric junction, at the distal esophagus, and in Barrett esophagus. However, the pathogenesis of this entity is still unclear. Whereas some authors have suggested that PACM is an acquired process others have raised the possibility of PACM being congenital in nature. Our results suggest that the duration of vonoprazan administration at a dose of 4 mg/kg plays an important role in the development of PACM.

Long-term potassium-competitive acid blockers administration causes microbiota changes in rats.

BACKGROUND: Vonoprazan is a new potassium-competitive acid blocker (P-CAB) that was recently approved by the FDA. It is associated with a fast onset of action and a longer acid inhibition time. Vonoprazan-containing therapy for helicobacter pylori eradication is highly effective and several studies have demonstrated that a vonoprazan-antibiotic regimen affects gut microbiota. However, the impact of vonoprazan alone on gut microbiota is still unclear.Please check and confirm the authors (Maria Cristina Riascos, Hala Al Asadi) given name and family name are correct. Also, kindly confirm the details in the metadata are correct.Yes they are correct.  METHODS: We conducted a prospective randomized 12-week experimental trial with 18 Wistar rats. Rats were randomly assigned to one of 3 groups: (1) drinking water as negative control group, (2) oral vonoprazan (4 mg/kg) for 12 weeks, and (3) oral vonoprazan (4 mg/kg) for 4 weeks, followed by 8 weeks off vonoprazan. To investigate gut microbiota, we carried out a metagenomic shotgun sequencing of fecal samples at week 0 and week 12.Please confirm the inserted city and country name is correct for affiliation 2.Yes it's correct. RESULTS: For alpha diversity metrics at week 12, both long and short vonoprazan groups had lower Pielou's evenness index than the control group (p = 0.019); however, observed operational taxonomic units (p = 0.332) and Shannon's diversity index (p = 0.070) were not statistically different between groups. Beta diversity was significantly different in the three groups, using Bray-Curtis (p = 0.003) and Jaccard distances (p = 0.002). At week 12, differences in relative abundance were observed at all levels. At phylum level, short vonoprazan group had less of Actinobacteria (log fold change = - 1.88, adjusted p-value = 0.048) and Verrucomicrobia (lfc = - 1.76, p = 0.009).Please check and confirm that the author (Ileana Miranda) and their respective affiliation 3 details have been correctly identified and amend if necessary.Yes it's correct. At the genus level, long vonoprazan group had more Bacteroidales (lfc = 5.01, p = 0.021) and Prevotella (lfc = 7.79, p = 0.001). At family level, long vonoprazan group had more Lactobacillaceae (lfc = 0.97, p = 0.001), Prevotellaceae (lfc = 8.01, p < 0.001), and less Erysipelotrichaceae (lfc = - 2.9, p = 0.029). CONCLUSION: This study provides evidence that vonoprazan impacts the gut microbiota and permits a precise delineation of the composition and relative abundance of the bacteria at all different taxonomic levels.

Activation of the JAK/STAT Pathway Leads to BRAF Inhibitor Resistance in BRAFV600E Positive Thyroid Carcinoma.

A subset of thyroid cancers, recurrent differentiated thyroid cancers and anaplastic thyroid cancer (ATC), are difficult to treat by thyroidectomy and systemic therapy. A common mutation in thyroid cancer, BRAFV600E, has targetable treatment options; however, the results have been disappointing in thyroid cancers compared with BRAFV600E melanoma, as thyroid cancers quickly become resistant to BRAFV600E inhibitor (BRAFi). Here, we studied the molecular pathway that is induced in BRAFV600E thyroid cancer cells and patient-derived tumor samples in response to BRAFi, vemurafenib, using RNA-sequencing and molecular analysis. Both inducible response to BRAFi and acquired BRAFi resistance in BRAFV600E thyroid cancer cells showed significant activation of the JAK/STAT pathway. Functional analyses revealed that the combination of BRAFi and inhibitors of JAK/STAT pathway controlled BRAFV600E thyroid cancer cell growth. The Cancer Genome Atlas data analysis demonstrated that potent activation of the JAK/STAT signaling was associated with shorter recurrence rate in patients with differentiated thyroid cancer. Analysis of tumor RNA expression in patients with poorly differentiated thyroid cancer and ATC also support that enhanced activity of JAK/STAT signaling pathway is correlated with worse prognosis. Our study demonstrates that JAK/STAT pathway is activated as BRAFV600E thyroid cancer cells develop resistance to BRAFi and that this pathway is a potential target for anticancer activity and to overcome drug resistance that commonly develops to treatment with BRAFi in thyroid cancer. IMPLICATIONS: Dual inhibition of BRAF and JAK/STAT signaling pathway is a potential therapeutic treatment for anticancer activity and to overcome drug resistance to BRAFi in thyroid cancer.