Prognosis of Reflux Symptom Resolution After Bariatric Surgery: How Can Preoperative Esophageal Testing Help?

PURPOSE: The incidence of unresolved postoperative reflux after bariatric surgery varies considerably. Consistent perioperative patient characteristics predictive of unresolved reflux remain unknown. We leverage our institution's comprehensive preoperative esophageal testing to identify predictors of postoperative reflux. MATERIALS AND METHODS: We performed a single-center retrospective review of adult patients with preoperative reflux symptoms who underwent either vertical sleeve gastrectomy (VSG) or Roux-en-Y gastric bypass (RYGB) from 2015 to 2021. All patients had pH and high-resolution manometry preoperatively. Predictors of postoperative unresolved reflux at 1 year were explored via Fisher's exact test, Kruskal Wallis test, and univariate logistic regression. RESULTS: Unresolved reflux was higher in patients undergoing VSG (n = 60/129,46.5%) vs. RYGB (n = 19/98, 19.4%). Median DeMeester scores were higher (22 vs. 13, p = .07) along with rates of ineffective esophageal motility (IEM) (31.6 vs. 8.9%, p = .01) in the 19 (19.3%) patients with unresolved postoperative reflux after RYGB compared to the resolved RYGB reflux cohort. Sixty (46.5%) of VSG patients had unresolved postoperative reflux. The VSG unresolved reflux cohort had similar median DeMeester and IEM incidence to the resolved VSG group but more preoperative dysphagia (13.3% vs. 2.9%, p = .04) and higher preoperative PPI use (56.7 vs. 39.1%, p = .05). In univariate analysis, only IEM was predictive of unresolved reflux after RYGB (OR 4.74, 95% CI 1.37, 16.4). CONCLUSION: Unresolved reflux was higher after VSG. Preoperative IEM predicted unresolved reflux symptoms after RYGB. In VSG patients, preoperative dysphagia symptoms and PPI use predicted unresolved reflux though lack of correlation to objective testing highlights the subjective nature of symptoms and the challenges in predicting postoperative symptomatology.

Esophageal Motility Patterns in Paraesophageal Hernia Patients Compared to Sliding Hiatal Hernia: Bigger Is Not Better.

BACKGROUND: In patients with paraesophageal hernias (PEH), the course of the esophagus is often altered, which may affect esophageal motility. High-resolution manometry (HRM) is frequently used to evaluate esophageal motor function prior to PEH repair. This study was performed to characterize esophageal motility disorders in patients with PEH as compared to sliding hiatal hernia and to determine how these findings affect operative decision-making. METHODS: Patients referred for HRM to a single institution from 2015 to 2019 were included in a prospectively maintained database. HRM studies were analyzed for the appearance of any esophageal motility disorder using the Chicago classification. PEH patients had confirmation of their diagnosis at the time of surgery, and the type of fundoplication performed was recorded. They were case-matched based on sex, age, and BMI to patients with sliding hiatal hernia who were referred for HRM in the same period. RESULTS: There were 306 patients diagnosed with a PEH who underwent repair. When compared to case-matched sliding hiatal hernia patients, PEH patients had higher rates of ineffective esophageal motility (IEM) (p<.001) and lower rates of absent peristalsis (p=.048). Of those with ineffective motility (n=70), 41 (59%) had a partial or no fundoplication performed during PEH repair. CONCLUSION: PEH patients had higher rates of IEM compared to controls, possibly due to a chronically distorted esophageal lumen. Offering the appropriate operation hinges on understanding the involved anatomy and esophageal function of each individual. HRM is important to obtain preoperatively for optimizing patient and procedure selection in PEH repair.

Type II hiatal hernias: do they exist or are they actually parahiatal hernias?

BACKGROUND: Type II hiatal hernias (HH) are characterized by a portion of the gastric fundus located above the esophageal hiatus adjacent to the esophagus while the gastroesophageal junction (GEJ) remains fixed below the esophageal hiatus. This type of HH has been called the "true" paraesophageal hernia (PEH) because the fundus appears to the side of the esophagus. In our experience, Type II HHs are occasionally identified on radiographic testing, however they are rarely, if ever, confirmed intraoperatively. This led to our question: Does Type II HH exist? METHODS: We searched for evidence of type II HH in three locations: 1. Retrospective review of all first-time PEH repairs (excluding Type I HHs and re-operative cases) performed at the University of Washington Medical Center from 1994 to 2021; 2. Operative videos available on YouTube and WebSurg websites; and 3. Abstracts from the SAGES annual meetings from 2005 to 2021. RESULTS: We found no evidence of Type II HH in any of our three searches. We performed 846 PEH repairs: 760 Type III, 75 Type IV, and 11 parahiatal. Upon website video review, we found only one possible type II hernia, though it too was likely a para-hiatal hernia. No video or case presentations of a type II HH were identified within SAGES annual meeting abstracts. CONCLUSION: Type II HHs do not exist as they are currently defined. Although uncommon, parahiatal hernia can easily be misinterpreted as Type II HH. We should consider changing the hiatal hernia classification system to prevent ongoing clinical confusion.

Characteristics and outcomes of patients undergoing paraesophageal hernia repair with selective use of biologic mesh.

BACKGROUND: The use of biologic mesh in paraesophageal hernia repair (PEHR) has been associated with decreased short-term recurrence but no statistically significant difference in long-term recurrence. Because of this, we transitioned from routine to selective use of mesh for PEHR. The aim of this study was to examine our indications for selective mesh use and to evaluate patient outcomes in this population. METHODS: We queried a prospectively maintained database for patients who underwent laparoscopic PEHR with biologic mesh from October 2015 to October 2018, then performed a retrospective chart review. The decision to use mesh was made intraoperatively by the surgeon. Recurrence was defined as the presence of > 2 cm intrathoracic stomach on postoperative upper gastrointestinal (UGI) series. RESULTS: Mesh was used in 61/169 (36%) of first-time PEHRs, and in 47/82 (57%) of redo PEHRs. Among first-time PEHRs, the indications for mesh included hiatal tension (85%), poor crural tissue quality (11%), or both (5%). Radiographic recurrence occurred in 15% of first-time patients (symptomatic N = 2, asymptomatic N = 3). There were no reoperations for recurrence. Among redo PEHRs, the indication for mesh was most commonly the redo nature of the repair itself (55%), but also hiatal tension (51%), poor crural tissue quality (13%), or both (4%). Radiographic recurrence occurred in 21% of patients (symptomatic N = 4, asymptomatic N = 1). There was 1 reoperation for recurrence in the redo-repair group. CONCLUSIONS: We selectively use biologic mesh in a third of our first-time repair patients and in over half of our redo-repair patients when there is a perceived high risk of recurrence based on hiatal tension, poor tissue quality, or prior recurrence. Despite the high risk for radiologic recurrence, there was only 1 reoperation for recurrence in the entire cohort.

The impact of bariatric surgery on esophageal function.

Obesity is a worldwide epidemic. There is increasing evidence that obesity is associated with benign gastroesophageal disease, including gastroesophageal reflux disease (GERD) and esophageal dysmotility. Bariatric surgery-including sleeve gastrectomy, gastric bypass, and adjustable gastric band placement-can effectively result in weight loss and control of obesity-related conditions, including GERD. However, there is increasing evidence that bariatric surgery itself can have a deleterious effect on esophageal function. In this review, we address the effect of obesity and bariatric surgery on esophageal dysfunction.

The use of crural relaxing incisions with biologic mesh reinforcement during laparoscopic repair of complex hiatal hernias.

INTRODUCTION: Laparoscopic hiatal hernia repair has a better chance of success if the hiatus is closed without tension. This study attempts to answer the following questions: (1) What is the rate of hiatal hernia recurrence in patients who undergo hiatal closure with diaphragmatic relaxing incisions? (2) Can biologic mesh be safely substituted for synthetic mesh as coverage of the relaxing incisions? METHODS: We identified all patients who underwent laparoscopic hiatal hernia repair at our institution between 2007 and 2013 and reviewed their clinical records. Radiologic recurrence was identified by an experienced radiologist and defined as the presence of any abdominal contents located above the diaphragm on esophagram. Clinical recurrence was defined as little or no improvement in symptoms, the development of a new symptom, or the need for medical, endoscopic, or surgical treatment of postoperative symptoms. RESULTS: A minimum of 6 months of radiologic and clinical follow-up was available for 146 (40 %) patients, including 16 with relaxing incisions. There were 66 (45 %) recurrent hernias detected on esophagram. There was no difference in the rate of recurrent hiatal hernia among the three groups: Primary closure of the hiatus (21/36 [58 %]), primary closure with biologic mesh reinforcement (36/94 [38 %]), and relaxing incision with biologic mesh reinforcement (9/16 [56 %]; p = 0.428). Two reoperations were performed on patients who underwent left relaxing incisions and developed symptomatic diaphragmatic hernias through the left relaxing incisions. There were no complications associated with use of biologic mesh at the hiatus. CONCLUSIONS: Rate of recurrent hiatal hernia is similar between patients who undergo diaphragmatic relaxing incisions and patients who undergo primary hiatal closure. Relaxing incisions can be safely performed on either crus; however, biologic mesh should not be used to patch a left-sided relaxing incision due to the risk of developing a diaphragmatic hernia.

Surgical treatment of gastroesophageal reflux disease.

Operative treatment of GERD has become more common since the introduction of LARS. Careful patient selection based on symptoms, response to medical therapy, and preoperative testing will optimize the chances for effective and durable postoperative control of symptoms. Complications of the LARS are rare and generally can be managed without reoperation. When reoperation is necessary for failed antireflux surgery, it should be performed by high-volume gastroesophageal surgeons.

Laparoscopic gastropexy relieves symptoms of obstructed gastric volvulus in highoperative risk patients.

BACKGROUND: Operative repair of obstructive gastric volvulus is challenging. In high-operative risk patients with obstructive gastric volvulus, we perform laparoscopic reduction of gastric volvulus and anterior abdominal wall sutured gastropexy. This case series reports our experience with this operation. METHODS: We reviewed the charts of all patients who presented with obstructive gastric volvulus and underwent laparoscopic gastropexy between 2007 and 2013. RESULTS: Eleven patients underwent laparoscopic gastropexy. Median age was 83 years (50 to 92). Six patients presented with chronic obstruction; 5 presented with acute obstruction. Median postoperative hospitalization was 2 days (1 to 39). Two patients required reoperation for displaced gastrostomy tubes. At median follow-up of 3 months (2 weeks to 57 months), all patients remained free of gastric obstructive symptoms and recurrent episodes of volvulus. Only 1 patient received nutrition via gastrostomy tube. CONCLUSIONS: Laparoscopic gastropexy can treat obstructed gastric volvulus in highoperative risk patients. Because of associated morbidity, gastrostomy tubes should be placed selectively.

Lack of evidence for a remote effect of renal ischemia/reperfusion acute kidney injury on outcome from temporary focal cerebral ischemia in the rat.

OBJECTIVE: Acute kidney injury (AKI) and ischemic stroke may occur in the same cardiac surgical patient. It is not known if an interaction exists between these organ injuries. Isolated renal ischemia/reperfusion is associated with dysfunction in remote, otherwise normal organs, including the brain. In a rat model of simultaneous bilateral renal artery occlusion (BRAO) and middle cerebral artery occlusion (MCAO), the authors tested the hypothesis that AKI would worsen experimental stroke outcome. DESIGN: Sixty thermoregulated anesthetized rats were randomized to (1) 40-minute BRAO, (2) 80-minute MCAO, or (3) simultaneous BRAO + MCAO. Serum creatinine was measured at baseline and 2 and 7 days after organ reperfusion. Neurologic function and brain and kidney histologies were measured on day 7. In a parallel study, serum cytokines were measured over 16 hours. SETTING: Laboratory. PARTICIPANTS: Male Wistar rats. INTERVENTIONS: Combined or isolated BRAO and MCAO. MEASUREMENTS AND MAIN RESULTS: AKI was similar between the BRAO and BRAO + MCAO groups, with greater 48-hour creatinine increases (p < 0.02) and renal histopathologic scores (p < 0.001) in these groups than with MCAO alone. Neurologic scores correlated with cerebral infarct size (p = 0.0001). There were no differences in neurologic score (p = 0.53) and cerebral infarct volume (p = 0.21) between the MCAO and BRAO + MCAO groups. There was no association between cerebral infarct size or neurologic score and 48-hour creatinine increase. Interleukin-6 was increased during reperfusion (p < 0.0001), but a difference among groups was absent (p = 0.41). CONCLUSIONS: In contrast to the effects reported for AKI on normal remote organs, AKI had no influence on infarct size or neurologic function after experimental ischemic cerebral stroke.

Effects of age, race, and sex on door-to-electrocardiogram time in emergency department non-ST elevation acute coronary syndrome patients.

BACKGROUND: Chest pain is a frequent complaint in the Emergency Department (ED), and an electrocardiogram (ECG) should be performed quickly to detect acute ST-segment elevation myocardial infarction. Previous studies have demonstrated disparities in cardiovascular care due to factors such as age, race, or sex; these studies have used non-homogenous populations across multiple sites of treatment, which may confound their results. STUDY OBJECTIVE: Our hypothesis was that, within a single center, demographic characteristics would not influence door-to-ECG time in ED patients with non-ST elevation acute coronary syndrome (NSTACS). METHODS: We performed a retrospective cohort study of patients presenting to the ED with NSTACS, requiring ECG changes or elevated cardiac biomarkers for inclusion, between 2001 and 2005. Multiple variable linear regression was used to evaluate the impact of race, sex, and age on door-to-ECG time. RESULTS: There were 247 patients who met inclusion criteria over the study period. The mean age was 62 ± 14 years; 159 (64%) were white, and 151 (61%) were male. The mean time to ECG was 25.6 ± 32.4 min. Neither age, sex, nor race had a significant impact on door-to-ECG time in either univariate or multiple variable modeling. A full model including age, sex, and race as well as all potential two-way interactions had minimal predictive ability (R(2) = 0.015). CONCLUSION: Within a single center, demographic characteristics had no impact on door-to-ECG performance time. We follow with a discussion of statistical methods available to adjust for clustering of observations in multicenter trials.

Simvastatin and atorvastatin improve behavioral outcome, reduce hippocampal degeneration, and improve cerebral blood flow after experimental traumatic brain injury.

The treatment of traumatic brain injury (TBI) remains limited, and aside from surgical hematoma evacuation, clinical management is largely supportive and directed toward management of cerebral edema and intracranial hypertension. Secondary neuronal injury caused by ischemia and the development of cerebral edema may occur in the subacute phase, with intracranial pressures often peaking in the first several days following injury. Because inflammation contributes significantly to the pathophysiology of cerebral ischemia and endothelial dysfunction underlies the development of cerebral edema, therapeutic strategies that target the post-traumatic inflammatory cascade and reduce endothelial dysfunction hold enormous potential to improve clinical outcomes after TBI. Statins inhibit inflammation by suppressing inflammatory cytokine release, and by interfering with multiple steps of leukocyte recruitment and migration into the CNS. In this study, we demonstrate that treatment with atorvastatin and simvastatin markedly reduced functional neurological deficits after traumatic brain injury in mice. These effects were accompanied by histological reduction in degenerating hippocampal neurons and suppression of inflammatory cytokine mRNA expression in brain parenchyma. Furthermore, statin treatment improved cerebral hemodynamics following head injury. Thus, the administration of statins may represent a viable therapeutic strategy in the acute treatment of closed head injury.

Isoflurane provides long-term protection against focal cerebral ischemia in the rat.

BACKGROUND: Long-term neuroprotection by isoflurane has been questioned. The authors examined factors in experimental models potentially critical to definition of enduring isoflurane neuroprotection. METHODS: Rats were prepared for temporary middle cerebral artery occlusion (MCAO). Pericranial normothermia was maintained. Neurologic deficits (range, 0-48; 0=no deficit) and cerebral infarct volumes were measured. In experiment 1, rats underwent 50 or 80 min MCAO while awake or anesthetized with 1.8% isoflurane. Blood pressure was controlled with phenylephrine. Outcome was evaluated 2 weeks later. In experiment 2, rats underwent 50 min MCAO while awake or anesthetized with isoflurane, with outcome evaluated 8 weeks later. In experiment 3, rats underwent 50 min MCAO while awake or anesthetized with isoflurane and 2 weeks recovery. Effects of phenylephrine and the mitochondrial adenosine triphosphate-sensitive K channel antagonist 5-hydroxydecanoate were studied. In experiment 4, isoflurane-anesthetized rats underwent 50 min MCAO with permanent or temporary common carotid artery occlusion, with outcome evaluated 2 weeks later. RESULTS: In experiment 1, isoflurane reduced neurologic deficit (median+/-interquartile range; awake vs. isoflurane: 11+/-12 vs. 8+/-6 for 80 min and 13+/-4 vs. 3+/-9 for 50 min; P=0.0006) and infarct size (160+/-97 vs. 84+/-62 mm for 80 min and 169+/-78 vs. 68+/-61 mm for 50 min; P<0.0001). In experiment 2, isoflurane protection persisted at 8 weeks after ischemia. In experiment 3, there was no effect of phenylephrine or 5-hydroxydecanoate. In experiment 4, permanent common carotid ligation increased infarct size threefold versus temporary occlusion. CONCLUSIONS: Isoflurane repeatedly improved long-term neurologic and histologic outcome from focal ischemia independent of ischemia duration, perfusion pressure, or pretreatment with 5-hydroxydecanoate.

The genetic determinants of renal impairment following cardiac surgery.

Cardiac surgery is frequently performed, and acute renal dysfunction is a common adverse event following this procedure. Cardiac surgery-related renal injury independently predicts longer hospital stays and greater rates of morbidity and mortality. Although much work has been completed toward better understanding of this phenomenon, the state of knowledge concerning surgery-related renal injury remains limited. Currently, there is no effective paradigm to identify patients who are at risk for this condition; the specific mechanisms of renal injury during surgery are incompletely understood; and few therapies exist to prevent or treat this phenomenon. To better understand this common clinical problem, recent research has focused on the importance of genetic variability within the physiological and patho-physiological systems that underlie renal dysfunction following cardiac surgery. Emphasizing the importance of using genetics to elucidate molecular mechanisms of this disease, this article reviews the current literature on genetic polymorphisms and post cardiac surgery-related renal dysfunction.

Probing substrate binding to metallo-beta-lactamase L1 from Stenotrophomonas maltophilia by using site-directed mutagenesis.

BACKGROUND: The metallo-beta-lactamases are Zn(II)-containing enzymes that hydrolyze the beta-lactam bond in penicillins, cephalosporins, and carbapenems and are involved in bacterial antibiotic resistance. There are at least 20 distinct organisms that produce a metallo-beta-lactamase, and these enzymes have been extensively studied using X-ray crystallographic, computational, kinetic, and inhibition studies; however, much is still unknown about how substrates bind and the catalytic mechanism. In an effort to probe substrate binding to metallo-beta-lactamase L1 from Stenotrophomonas maltophilia, nine site-directed mutants of L1 were prepared and characterized using metal analyses, CD spectroscopy, and pre-steady state and steady state kinetics. RESULTS: Site-directed mutations were generated of amino acids previously predicted to be important in substrate binding. Steady-state kinetic studies using the mutant enzymes and 9 different substrates demonstrated varying Km and kcat values for the different enzymes and substrates and that no direct correlation between Km and the effect of the mutation on substrate binding could be drawn. Stopped-flow fluorescence studies using nitrocefin as the substrate showed that only the S224D and Y228A mutants exhibited weaker nitrocefin binding. CONCLUSIONS: The data presented herein indicate that Ser224, Ile164, Phe158, Tyr228, and Asn233 are not essential for tight binding of substrate to metallo-beta-lactamase L1. The results in this work also show that Km values are not reliable for showing substrate binding, and there is no correlation between substrate binding and the amount of reaction intermediate formed during the reaction. This work represents the first experimental testing of one of the computational models of the metallo-beta-lactamases.