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.

Patterns in the Reporting of Aggressive Histologic Subtypes in Papillary Thyroid Cancer.

INTRODUCTION: The tall cell, columnar, and diffuse sclerosing subtypes are aggressive histologic subtypes of papillary thyroid cancer (PTC) with increasing incidence, yet there is a wide variation in reporting. We aimed to identify and compare factors associated with the reporting of these aggressive subtypes (aPTC) to classic PTC (cPTC) and secondarily identify differences in outcomes. METHODS: The National Cancer Database was utilized to identify cPTC and aPTC from 2004 to 2017. Patient and facility demographics and clinicopathologic variables were analyzed. Independent predictors of aPTC reporting were identified and a survival analysis was performed. RESULTS: The majority of aPTC (67%) were reported by academic facilities. Compared to academic facilities, all other facility types were 1.4-2.0 times less likely to report aPTC (P < 0.05). Regional variation in reporting was noted, with more cases reported in the Middle Atlantic, despite there being more total facilities in the South Atlantic and East North Central regions. Compared to the Middle Atlantic, all other regions were 1.4-5 times less likely to report aPTC (P < 0.001). Patient characteristics including race and income were not associated with aPTC reporting. Compared to cPTC, aPTC had higher rates of aggressive features and worse 5-y overall survival (90.5% versus 94.5%, log rank P < 0.001). CONCLUSIONS: Aggressive subtypes of PTC are associated with worse outcomes. Academic and other facilities in the Middle Atlantic were more likely to report aPTC. This suggests the need for further evaluation of environmental or geographic factors versus a need for increased awareness and more accurate diagnosis of these subtypes.

Evaluation of factors associated with reflux recurrence after fundoplication.

INTRODUCTION: Reflux recurrence after fundoplication remains poorly understood, prompting an investigation into factors associated with it. METHODS: A study was conducted to review patients who had primary fundoplication. The main focus was on identifying recurrent reflux confirmed by an abnormal DeMeester score of > 14.7. Risk factors were evaluated using multivariable logistic regression. Additionally, Impedance planimetry (EndoFLIP™) measurements were taken into account if performed during the operation. RESULTS: Out of 137 patients who met inclusion criteria. 17 (12.4%) patients developed recurrent reflux, with 6.5% of them required secondary fundoplication. There were no significant differences in demographic, pre-operative or intra-operative characteristics between patients who developed recurrent reflux and those who did not (p > 0.05). However, in the subset of patients who underwent EndoFLIP™ monitoring during surgery (60%); patients who developed recurrent reflux had lower HPZ values post-wrap compared to those who did not [3.5 IQR (3-4) vs 2.5 IQR (1.8-3), p < 0.01]. Patient factors such as age, sex, BMI, and race were not found to be associated with recurrent reflux or reflux requiring surgical re-intervention in our analysis. However, having a low HPZ post-wrap was identified as a risk factor for recurrent reflux [0.15 95% CI (0.03-0.57)] and it showed a significant correlation with post-operative DeMeester score [r = - 0.28, p = 0.02]. CONCLUSION: No relationship was found between patient factors such as age, sex, race, and BMI and recurrent reflux following primary fundoplication. However, a Low HPZ post-wrap was a risk factor for recurrent reflux with a risk ratio of 0.15 (0.03-0.57) and a p value of 0.01. Larger studies are needed to evaluate the impact of HPZ on outcomes following fundoplication in order to develop guidelines for clinicians.

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.

Perineural Invasion in Papillary Thyroid Cancer: A Rare Indicator of Aggressive Disease.

BACKGROUND: Perineural invasion (PNI) is associated with aggressive tumor behavior, increased locoregional recurrence, and decreased survival in many carcinomas. However, the significance of PNI in papillary thyroid cancer (PTC) is incompletely characterized. METHODS: Patients diagnosed with PTC and PNI from 2010-2020 at a single, academic center were identified and matched using a 1:2 scheme to patients without PNI based on gross extrathyroidal extension (ETE), nodal metastasis, positive margins, and tumor size (±4 cm). Mixed and fixed effects models were used to analyze the association of PNI with extranodal extension (ENE)-a surrogate marker of poor prognosis. RESULTS: In total, 78 patients were included (26 with PNI, 52 without PNI). Both groups had similar demographics and ultrasound characteristics preoperatively. Central compartment lymph node dissection was performed in most patients (71%, n = 55), and 31% (n = 24) underwent a lateral neck dissection. Patients with PNI had higher rates of lymphovascular invasion (50.0% vs. 25.0%, p = 0.027), microscopic ETE (80.8% vs. 44.0%, p = 0.002), and a larger burden [median 5 (interquartile range [IQR] 2-13) vs. 2 (1-5), p = 0.010] and size [median 1.2 cm (IQR 0.6-2.6) vs. 0.4 (0.2-1.4), p = 0.008] of nodal metastasis. Among patients with nodal metastasis, those with PNI had an almost fivefold increase in ENE [odds ratio [OR] 4.9 (95% confidence interval [CI] 1.5-16.5), p = 0.008] compared with those without PNI. More than a quarter (26%) of all patients had either persistent or recurrent disease over follow-up (IQR 16-54 months). CONCLUSIONS: PNI is a rare, pathologic finding that is associated with ENE in a matched cohort. Additional investigation into PNI as a prognostic feature in PTC is warranted.

Coexisting Papillary and Anaplastic Thyroid Cancer: Elucidating the Spectrum of Aggressive Behavior.

BACKGROUND: Anaplastic thyroid carcinoma (ATC) is a rare and lethal form of thyroid cancer. Overall prognosis is unclear when it arises focally in a background of papillary thyroid cancer (PTC). Clinicopathologic features and outcomes of tumors with coexisting PTC and ATC histologies (co-PTC/ATC) were categorized. METHODS: The National Cancer Database was queried for histologic codes denoting PTC, ATC, and co-PTC/ATC, defined as Grade 4 PTC, diagnosed from 2004 to 2017. Clinicopathologic features, OS, and treatment outcomes were analyzed by histologic type. RESULTS: A total of 386,862 PTC, 763 co-PTC/ATC, and 3,880 ATC patients were identified. Patients with co-PTC/ATC had clinicopathologic features in-between those of PTC and ATC, including rates of tumor size >4 cm, extrathyroidal extension, and distant metastases. On multivariable Cox proportional hazards modeling, age >55 years, Charlson-Deyo score ≥2, positive lymph nodes, lymphovascular invasion, distant metastases, and positive surgical margins were associated with worse OS, whereas radioactive iodine (RAI) and external beam radiation therapy (EBRT) were associated with improved OS, irrespective of margin status. OS was worse for co-PTC/ATC than for PTC but better than for ATC and differed based on the presence or absence of "aggressive" tumor features, including lymph node positivity, lymphovascular invasion, distant metastases, and positive surgical margins. CONCLUSIONS: Survival of patients with co-PTC/ATC is dependent on the presence of aggressive clinicopathologic features and lies within a spectrum between that of PTC and ATC. Adjuvant RAI and EBRT treatment may be beneficial, even after R0 resection.

Treatment of Secondary Hyperparathyroidism and Posttransplant Tertiary Hyperparathyroidism.

INTRODUCTION: Secondary hyperparathyroidism (sHPT) is prevalent in dialysis patients and can lead to tertiary hyperparathyroidism (tHPT) after kidney transplantation. We aimed to assess the association of pretransplant sHPT treatment on posttransplant outcomes. METHODS: We reviewed kidney transplant patients treated with parathyroidectomy or cinacalcet for sHPT. We compared patients biochemical and clinical parameters, and outcomes based on sHPT treatment. RESULTS: A total of 41 patients were included: 18 patients underwent parathyroidectomy and 23 patients received cinacalcet prior to transplantation. There were no significant differences between demographics, comorbidities, allograft characteristics or pre-sHPT intervention parathyroid hormone (PTH) and calcium levels. Patients that underwent parathyroidectomy were on dialysis for longer, although not significantly (71.9 versus 42.3 mo, P = 0.051). At time of transplantation, patients treated by parathyroidectomy had increased rates of controlled sHPT (88.9%; 16/18 versus 47.8%; 11/23, P = 0.008). Patients treated by parathyroidectomy had decreased development of tHPT (5.9%; 1/17; versus 42.1%; 8/19, P = 0.020) as well as decreased rates of posttransplant treatment with cinacalcet (11.1%; 2/18 versus 52.2%; 12/23, P = 0.008). Three patients treated with cinacalcet underwent parathyroidectomy after transplantation. Median PTH after transplant remained lower in patients treated by parathyroidectomy prior to transplant compared to those treated with cinacalcet (60.7 [interquartile range 39.7-133.4] versus 170.0 [interquartile range 128.4-292.7], P = 0.001). Allograft function and survival were similar for parathyroidectomy and cinacalcet, with median follow-up after transplantation of 56.7 and 34.2 mo, respectively. CONCLUSIONS: sHPT treated by parathyroidectomy is associated with controlled PTH levels at transplantation and decreased rates of tHPT. Long-term outcomes should be studied on a larger scale.

Quantifying physiologic parameters of the gastroesophageal junction during robotic sleeve gastrectomy and identifying predictors of post-sleeve gastroesophageal reflux disease.

BACKGROUND: Sleeve gastrectomy is among the most commonly-performed procedures for morbid obesity. However, patients occasionally develop post-sleeve gastroesophageal reflux disease (GERD). Identifying patients most at risk for this complication remains difficult. We aimed to correlate intra-operative physiologic measurements of the lower esophageal sphincter (LES) at the gastroesophageal junction (GEJ) during robotic sleeve gastrectomy in an attempt to identify predictors of post-sleeve GERD symptoms. METHODS: A retrospective chart review of a prospectively maintained database identified 28 patients in whom robotic sleeve gastrectomy was performed utilizing EndoFLIP™ technology between January and September 2021. Intraoperative LES measurements at the GEJ including cross-sectional area (CSA), distensibility index (DI), intra-balloon pressure, and high-pressure zone (HPZ length) were correlated with post-operative GERD. RESULTS: GEJ CSA, pressure, and DI increased over the course of the surgery (CSA pre-op: 31 (IQR 19.3-39.5) mm2 vs. post-op: 67 (IQR 40.8-95.8) mm2, p < 0.001; pressure: 25.8 (IQR 20.2-33.1) mmHg vs. 31.5 (IQR 28.9-37.0) mmHg, p = 0.007; DI 1.1 (IQR 0.8-1.8) mm2/mmHg vs. 2.0 (IQR 1.2-3.0) mm2/mmHg, p = < 0.001), whereas HPZ length decreased (2.5 (IQR 2.5-3) cm vs. 2.0 (IQR 1.3-2.5) cm, p = 0.022). Twenty-three patients (82.1%) completed a post-operative GERD questionnaire. Fifteen (65.2%) had no GERD symptoms before or after surgery; 5 (21.7%) reported new post-sleeve GERD symptoms; 3 (13.0%) reported exacerbation of pre-existing GERD symptoms. Patients with new or worsening GERD symptoms had higher post-sleeve DIs (3.2 (IQR 1.9-4.5) mm2/mmHg vs. 1.5 (IQR 1.2-2.4) mm2/mmHg, p = 0.024) and lower post-sleeve LES pressures (29.9 (IQR 26.3-32.9) mmHg vs. 35.2 (IQR 31.0-38.0) mmHg, p = 0.023) than those without. CONCLUSIONS: An increase in GEJ CSA, pressure, and DI, and a decrease in GEJ length can be expected during robotic sleeve gastrectomy. Patients with new or worsening post-sleeve GERD symptoms have higher post-sleeve DI and lower post-sleeve LES pressure than their asymptomatic counterparts.

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.

Transoral incisionless fundoplication for recurrent symptoms after laparoscopic fundoplication.

BACKGROUND: Revision of a failed laparoscopic fundoplication carries higher risk of complication and lower chance of success compared to the original surgery. Transoral incisionless fundoplication (TIF) may be an endoscopic alternative for select GERD patients without need of a moderate/large hiatal hernia repair. The aim of this study was to assess feasibility, efficacy, and safety of TIF 2.0 after failed laparoscopic Nissen or Toupet fundoplication (TIFFF). METHODS: This is a multicenter retrospective cohort study of patients who underwent TIFFF between September 2017 and December 2020 using TIF 2.0 technique (EsophyX Z/Z+) performed by gastroenterologists and surgeons. Patients were included if they had (1) recurrent GERD symptoms, (2) pathologic reflux based upon pH testing or Grade C/D esophagitis or Barrett's esophagus, and (3) hiatal hernia ≤ 2 cm. The primary outcome was improvement in GERD Health-Related Quality of Life (GERD-HRQL) post-TIFFF. The TIFFF cohort was also compared to a similar surgical re-operative cohort using propensity score matching. RESULTS: Twenty patients underwent TIFFF (median 4.1 years after prior fundoplication) and mean GERD-HRQL score improved from 24.3 ± 22.9 to 14.75 ± 21.6 (p = 0.014); mean Reflux Severity Index (RSI) score improved from 14.1 ± 14.6 to 9.1 ± 8.0 (p = 0.046) with 8/10 (80%) of patients with normal RSI (< 13) post-TIF. Esophagitis healed in 78% of patients. PPI use decreased from 85 to 55% with 8/20 (45%) patients off of PPI. Importantly, mean acid exposure time decreased from 12% ± 17.8 to 0.8% ± 1.1 (p = 0.028) with 9/9 (100%) of patients with normalized pH post-TIF. There were no statistically significant differences in clinical efficacy outcomes between TIFFF and surgical revision, but TIFFF had significantly fewer late adverse events. CONCLUSION: Endoscopic rescue with TIF is a safe and efficacious alternative to redo laparoscopic surgery in symptomatic patients with appropriate anatomy and objective evidence of persistent or recurrent reflux.

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.

Exposure to Polybrominated Diphenyl Ether Flame Retardants Causes Deoxyribonucleic Acid Damage in Human Thyroid Cells In Vitro.

INTRODUCTION: The incidence of papillary thyroid cancer (PTC) in the United States has tripled in the past 30 y. Polybrominated diphenyl ethers (PBDEs) are flame retardants that were ubiquitously used over that time period, and exposure to PBDEs has been associated with PTC prevalence. They are potential carcinogens via their induction of reactive oxygen species (ROS) formation and resultant deoxyribonucleic acid (DNA) damage. We sought to determine the effects of PBDE and tris(2-chloroethyl) phosphate (TCEP), another flame retardant implicated in PTC incidence, on thyrocytes in vitro and measure PBDE levels in human thyroid tissue to determine their carcinogenic potential. METHODS: Nthy-Ori, an immortalized benign human thyroid follicular cell line was used as a model of normal human thyroid. MTT assays were used to measure cell viability after exposure to PBDEs and TCEP. ROS levels and double-stranded and single-stranded DNA breaks were measured to determine genotoxicity. DNA damage response protein levels were measured with immunoblotting. RESULTS: Exposure to 20µM PBDE or TCEP for 48 h had minimal effects on thyrocyte viability. There was no significant increase in intracellular ROS up to 6 h following PBDE or TCEP exposure in thyrocytes; however, cells exposed to PBDE 47 showed evidence of DNA single-stranded and double-stranded breaks. There was a dose-dependent increase in γH2AX levels following exposure to PBDEs 47 and 209 in Nthy-Ori cells but not with TCEP treatment. CONCLUSIONS: PBDE 47 and 209 demonstrated genotoxicity but not cytotoxicity in follicular thyrocytes in vitro. Therefore, PBDE 47 and 209 may be carcinogenic in human thyroid cells.

Risk factors for venous thromboembolism (VTE) after adrenalectomy for adrenal cortical neoplasms.

BACKGROUND: Incidence of venous thromboembolism (VTE) after adrenalectomy for adrenal cortical carcinoma (ACC) is unknown. Herein, we aim to identify the relative incidence and risk factors of VTE after adrenalectomy for ACC. METHODS: The American College of Surgeons National Surgical Quality Improvement Program database was queried to identify patients who underwent adrenalectomy for ACC, Cushing syndrome (CS), and benign adrenal cortical syndromes (BACS). Univariable and multivariable analyses were used to determine clinical characteristics, 30-day postoperative VTE occurrences, and associated risk factors. Khorana oncologic risk score (KRS) for VTE was calculated and compared between groups. RESULTS: A total of 5896 patients were analyzed: 576 ACC, 371 CS, and 4949 BACS. Postoperative VTE occurred 0.9%, with the highest rate occurring in ACC (2.6% ACC vs. 1.6% CS vs. 0.7% BACS, p < 0.001). Forty percent of VTEs in the ACC cohort were diagnosed postdischarge. ACC patients with KRS ≥ 2 had a 9.6% incidence of VTE (p = 0.007). Multivariable analysis identified increased age (p = 0.03), presence of adrenal cancer (p = 0.01), and KRS ≥ 2 (p = 0.005) as risk factors for VTE after adrenalectomy. CONCLUSIONS: Postoperative VTE after adrenalectomy occurs most frequently for ACC. ACC patients with increased age and/or Khorana score ≥2 should be considered for extended VTE prophylaxis.

The impact of pneumoperitoneum on esophagogastric junction distensibility during anti-reflux surgery.

OBJECTIVE: We aimed to quantify the contribution of pneumoperitoneum on compliance of the esophagogastric junction (EGJ) during anti-reflux surgery. BACKGROUND: Compliance of the EGJ is reduced with anti-reflux surgery. EndoFLIP® planimetry can be used to assess dynamic changes of EGJ compliance intraoperatively. It is unclear how pneumoperitoneum impacts intraoperative measurements by EndoFLIP® and the implications thereof on validity of the results. Therefore, determining variability in EndoFLIP® measurements based on pneumoperitoneum is warranted to establish guidelines to interpret clinical outcomes. METHODS: Primary anti-reflux surgery was performed on 39 consecutive patients with pathologic reflux. Intraoperative EGJ measurements including distensibility index (DI), cross-sectional area (CSA), and intrabag pressure were collected using EndoFLIP® at 0, 10, and 15 mmHg of intraperitoneal pressure. Data were acquired pre-procedure, post-hiatal hernia repair, and post-LES augmentation with fundoplications. RESULTS: Patients underwent Nissen (13.2%), Toupet (68.4%), LINX (10.5%), or Hill-fundoplications (7.9%). There was no difference between 0 and 10 mmHg of pneumoperitoneum in CSA, pressure, or DI measurements pre-procedure; however, there was a difference between 0 and 15 mmHg in pressure (p = 0.016) and DI (p = 0.023) measurements. After LES augmentation, 10 mmHg intraperitoneal pressure reduced DI, though the absolute difference is small (2.0 vs. 1.5 mm2/mmHg, p = 0.002). CONCLUSION: Pneumoperitoneum affected EGJ distensibility at 15 mmHg, but not 10 mmHg, of insufflation prior to anti-reflux procedures. After anti-reflux surgery, there was a significant variance between 0 and 10 mmHg of pneumoperitoneum in pressure and distensibility. The change in pressure appears linear and needs to be considered if procedural modifications are performed based on intraoperative findings and when evaluating clinical outcomes.

Quantifying physiologic parameters of the gastroesophageal junction during re-operative anti-reflux surgery.

BACKGROUND: Hiatal hernia re-approximation during index anti-reflux surgery (ARS) contributes approximately 80% of overall change in distensibility index (DI) and, potentially, compliance of the gastroesophageal (GEJ), while sphincter augmentation contributes approximately 20%. Whether this is seen in re-operative ARS is unclear. We quantify the physiologic parameters of the GEJ at each step of robotic re-operative ARS and compare these to index ARS. METHODS: Robotic ARS with hiatal hernia repair was performed on 195 consecutive patients with pathologic reflux utilizing EndoFLIP™, of which 26 previously had ARS. Intra-operative GEJ measurements, including cross-sectional area (CSA), pressure, DI, and high-pressure zone (HPZ) length were collected pre-repair, post-diaphragmatic re-approximation, post-mesh placement, and post-lower-esophageal sphincter (LES) augmentation. RESULTS: Both cohorts were similar by sex and BMI and underwent similar procedures. The re-operative cohort was older (60.6 ± 15.3 vs. 52.7 ± 16.2 years, p = 0.03), had more frequent pre-operative dysphagia (69.2% vs. 42.6%, p = 0.01) and esophageal dysmotility on barium swallow (75.0% vs. 35.0%, p < 0.001) but lower rates of hiatal hernia on endoscopy (30.8% vs. 68.7%, p < 0.001) compared to index procedures. Among the re-operative cohort, the CSA decreased by 34 (IQR - 80, - 15) mm2 and DI 1.1 (IQR - 2.4, - 0.6) mm2/mmHg (both p < 0.001). Pressure increased by 11.2 (IQR 4.7, 14.9) mmHg and HPZ by 1.5 (1,2) cm (both p < 0.001). These changes were similar to those seen in index ARS. Diaphragmatic re-approximation contributed to a greater percentage of overall change to the GEJ than did the augmentation procedure, with 72% of the change in DI occurring during hiatal closure, similar to that seen during index ARS. CONCLUSIONS: During re-operative ARS, dynamic intra-operative monitoring can quantify the effects of each operative step on GEJ physiologic parameters. Diaphragmatic re-approximation appears to have a greater effect on GEJ physiology than does LES-sphincter augmentation during both index and re-operative ARS.