Postsurgical gastroparesis (PSG) is a syndrome of objectively delayed gastric emptying without mechanical obstruction following a surgical intervention on the stomach or esophagus. It most commonly results from a surgical disruption of the vagal pathways innervating the stomach and pylorus. The symptoms most commonly associated with the syndrome are early satiety, nausea, vomiting, abdominal pain and bloating occurring early after a foregut operation. Classically, PSG developed as a result of a vagotomy for peptic ulcer disease, however in the current era it is more commonly associated with a variety of foregut and thoracic operations. Interestingly, not all patients who undergo truncal vagotomy without a gastric resection or drainage procedure will develop gastroparesis and likewise, some patients with intact vagus nerves can have PSG. It is estimated that 5–10% of patients who undergo intentional or inadvertent vagotomy, and 50% who undergo resection for gastric outlet obstruction, will develop gastroparesis . Although diabetic and idiopathic gastroparesis are more common, cases of PSG present a unique challenge in diagnosis and management. This chapter will review the epidemiology of PSG, clinical characteristics of the disease, and suggest strategies for diagnosis and management.
Epidemiology of PSG
The true incidence of postsurgical gastroparesis is difficult determine given that the majority of the literature on the subject is limited to retrospective case series. Additionally, much of the research on PSG comes from tertiary academic centers which likely treat only the most severe or complex cases of PSG . Many cases of PSG may be mild with symptoms controlled with dietary modification or medications. One of the best estimates of the incidence of PSG comes from a population-based study of Olmsted County, Minnesota. Over a ten year period the investigators identified 83 confirmed cases of gastroparesis of any cause with an incidence rate of 6.3 cases per 100,000 person-years, of which 7.2% of cases were related to a prior foregut operation . In one series of cases of gastroparesis referred to a tertiary center, PSG was the third most common cause accounting for 13% of all cases, compared with 29% of cases caused by diabetes and 36% which were idiopathic . The exact relation to surgery is further complicated by the fact that many patients operated on for foregut disorder, primarily GERD, may have had preexisting gastroparesis that was either subclinical or missed as the underlying cause of the reflux (so called “overflow reflux”).
Mechanism and pathophysiology
Post-surgical gastroparesis is most commonly the result of entrapment or division of the vagal nerves after a surgical procedure. Historically, vagotomy for peptic ulcer disease was the most common procedure associated with the development of PSG, however this operation is now performed rarely in the era of proton pump inhibitor therapy and treatment of Helicobacter pylori . Gastro/pyloric dysmotility is the end common pathway for PSG. Normal gastric empty relies on the vagal inputs to control gastric relaxation, stimulate contraction of the antrum and induce pyloric relaxation. Truncal vagotomy results in loss of gastric receptive relaxation which sometimes leads to rapid transit of a food bolus from the proximal to distal stomach causing early satiety and bloating. Loss of antral contraction and pyloric relaxation can cause food retention in the stomach . Ironically, the other common physiologic complication following vagotomy is dumping, which is characterized by too rapid emptying of the stomach. Recent studies using endoscopic impedance planimetry to measure the mechanical characteristics of the pylorus in patients with gastroparesis have found that pyloric diameter is inversely correlated with symptom intensity and that decreased pyloric compliance was associated with worse symptoms and quality of life suggesting that vagal inputs to the pylorus are critical in the development of PSG .
One theory regarding patients who experience vagal nerve injury and develop either delayed gastric emptying or dumping is that there are different vagal nerve injury patterns that impacts the innervation to the body and fundus differently than innervation to the antrum and pylorus. When the antrum and pylorus are spared, the loss of gastric reception/storage results in rapid transit of food into the duodenum and the development of dumping syndrome. In contrast, when inputs to both the antrum and body are disrupted the stomach is unable to emptying properly and gastroparesis develops. These findings are the basis for the highly selective vagotomy procedure which aims to reduce parietal cell innervation in the body to reduce acid secretion while maintaining pyloric innervation to preserve normal gastric emptying.
Other rarer causes of PSG are mechanical obstruction due to gastric outlet stricturing, which if chronic enough can result in progressive gastric motility failure or dysmotility caused by extensive perigastric adhesions, the so called “frozen stomach”. or post-gastric disruption of GI motility such as following duodenal resections.
Clinical characteristics and diagnosis
The symptoms of gastroparesis are similar regardless of the etiology . The diagnosis of PSG relies on a high index of suspicion. PSG should be suspected in any patient who has undergone an upper abdominal or thoracic operation and presents with symptoms of early satiety, postprandial bloating, abdominal pain, nausea or vomiting. In one study of 146 patient with objectively confirmed delayed gastric emptying nausea was present in 92%, vomiting in 84%, abdominal bloating in 75%, and early satiety in 60% . In many patients these symptoms are mild or transient however persistent or progressive symptoms warrant further investigation. The first step in the diagnostic evaluation of a patient with suspected gastroparesis is to rule out gastric outlet obstruction either endoscopically or fluoroscopically and to rule out exogenous causes of delayed gastric emptying such as medications or opioid use. Additionally, other diagnoses such as peptic ulcer disease, gastric cancer, bowel obstruction and biliary dysfunction should be considered as there is significant overlap in the symptoms of these diagnoses .
Gastric emptying can be objectively tested using either scintigraphy or a wireless motility capsule . For either of these tests, the patient should discontinue any medication which might impact gastric emptying including opioid medications or prokinetic agents. Scintigraphy is the conventional means of measuring gastric emptying. This test is performed by having the patient ingest a sulfur colloid labeled test meal and obtained serial images at the 0, 1, 2, 3 and 4-hour time points. Gastric retention of the radiotracer is measured; delayed retention is defined as >90% at 1 hour, >60% at 2 hours, and >10% gastric retention at 4 hours. The 4-hour parameter being the most reliable predictor of delayed gastric emptying . Wireless motility capsule testing is a newer technology in which the patient ingests a capsule which measure pH, pressure and temperature. These variables are used to determine the location of the capsule within the GI tract. The findings of this study have been shown to correlate well with traditional scintigraphy. The wireless motility capsule also provides information regarding small bowel and colonic transit times which, if abnormal, may influence the decision to proceed with surgical intervention .
Interpretation of objective gastric emptying studies can be challenging in the post-surgical patient as gastric emptying is likely significantly different from normal controls. Unfortunately, there are no standardized normal values for gastric emptying after gastroesophageal surgery and little information regarding expected values for symptomatic patients. After gastric resection the expected gastric function is a delay in the emptying of solids with rapid emptying of liquids, however the degree to which this occurs likely varies with the extent of gastric resection and method of reconstruction (Bilroth I or II vs Roux-en-y) . Additionally, fundoplication alone can result in accelerated emptying of both solids and liquids compared to normal controls . Inadvetant injury to the vagus nerves during fundoplication can however, lead to a different outcome,
Operations commonly associated with post-surgical gastroparesis
Peptic ulcer surgery
Gastroparesis developing after peptic ulcer surgery is the “classic” example of PSG. Most commonly this syndrome was described after truncal vagotomy with gastric resection and gastrojenunostomy. Interestingly the pattern of gastric dysfunction after these operations is variable depending on the type of vagotomy performed and the method of gastrointestinal reconstruction that is employed. A prospective randomized clinical trial of 152 patients compared proximal gastric vagotomy (PGV), truncal vagotomy with drainage (TV+D), and truncal vagotomy with antrectomy (TV+A) for the treatment of chronic duodenal ulcer. Postoperative gastric symptoms developed in all three groups but were generally worse in the TV+A group suggesting that larger gastric resection and less selective vagotomy may increase the risk of developing PSG . Furthermore, patients who undergo gastric resection for peptic ulcer disease causing gastric outlet obstruction are significantly more likely to develop PSG most likely due to chronic distention of the stomach resulting in permanent atonicity and motility loss .
Additionally, roux-en-y reconstruction after partial gastrectomy seems to have an adverse impact on gastric emptying independent of the impact of vagotomy. The roux limb has been shown to generate ectopic pacemaker activity which propagates to the stomach in a retrograde fashion, allowing the roux limb to cause a functional obstruction . This is the theoretical basis for jejunal implantable electric stimulation for patients with PSG after roux-en-y reconstruction, however this is not currently experimental and not used in clinical practice .
Patients presenting with symptoms of gastroparesis after antireflux surgery present a unique diagnostic and management challenge. In a large population-based database study, 3.8% of patients who underwent fundoplication later had a diagnosis of gastroparesis or a follow-up procedure to treat gastroparesis . There is overlap in the symptoms of GERD and gastroparesis such that without careful screening, one of the diagnoses may be missed. In a study of 615 patients who underwent Nissen fundoplication, 100% of patients had a least 1 gastrointestinal complaint during the first 3 months postoperatively, with Early satiety (88%), bloating/flatulence (64%), and dysphagia (34%) being the most common. However, by 1 year 94% of these symptoms had resolved . Patients with persistent symptoms after fundoplication warrant further investigation. Additionally, gastroparesis and GERD can be present in the same patient and gastroparesis exacerbates or even causes GERD due to abnormal emptying of the stomach. Patients presenting for GERD treatment who have a normal LES on manometry, are severe diabetics, or who have unusual symptoms such as bloating and nausea or gastric pain should be carefully evaluated for gastroparesis as antireflux surgery is likely to be both short lasting and make them miserable. The impact of a fundoplication on gastric emptying is complex. In one study of 81 patients who underwent a gastric emptying study prior to fundoplication found that patients who developed bothersome gas bloat syndrome were more likely to have preoperative delayed gastric emptying, suggesting that fundoplication may unmask underlying gastroparesis . Vagus nerve injury may also play a role in the development of PSG after fundoplication. In another study of 125 patient who underwent pre- and post-operative vagal nerve integrity testing with pancreatic polypeptide, 18% of patients showed evidence of vagal nerve trauma at 6 months post operatively and postoperative gastric emptying was significantly delayed in the vagus nerve injury group . However in the absence of vagus nerve injury, there is evidence that gastric emptying increases after fundoplication and patients with mild delays in gastric emptying may experience normalization after fundoplication making this a difficult clinical decision . Again, the recommendation is to be liberal ordering GES before fundoplication to avoid either a bad outcome and/or the fundoplication being blamed for postoperative symptoms of gastroparesis. We in fact recommend that patients with GERD and known DGE have a pyloroplasty along with their fundoplication to address both problems.
Pancreatic and hepatobiliary surgery are frequent causes of PSG, with pancreaticoduodenectomy (Whipple procedure) having the strongest association with this complication. In the acute post-operative setting many patients who have undergone a Whipple procedure experience delayed gastric emptying however nearly 20–50% have prolonged symptoms and develop true gastroparesis . In this instance, the proposed mechanism of the development of PSG is not vagus nerve injury but rather a disruption in the coordination of gastrointestinal motility due to the resection of the duodenum. Advanced or locally recurrent pancreatic cancer can also cause gastroparesis due to nerve involvement or organ encasement.
The sleeve gastrectomy and gastric bypass comprise the majority of bariatric operation performed today, with gastric bypass being more commonly associated with PSG. The incidence of gastroparesis after bariatric surgery is difficult to determine largely due to the fact that early satiety is a hallmark symptom of gastroparesis and an expected outcome after any restrictive bariatric operation. Solid gastric emptying is slower and liquid emptying is more rapid after gastric bypass surgery . The proposed mechanism of delayed gastric emptying is identical to that described above for roux-en-y reconstruction after peptic ulcer surgery. Sleeve gastrectomy, now the most common bariatric surgery performed, results in delayed esophageal transit but increases both solid and liquid emptying – sometimes to the point of causing dumping symptoms.
The incidence of clinically relevant delayed gastric emptying after esophagectomy with gastric conduit is approximately 10–20%, however up to 50% of patients will experience occasional symptoms of delayed gastric emptying . The exact incidence varies between studies based on the diagnostic test and cut off limit used, as well as the timing of post-operative testing. The cause of delayed gastric emptying after esophagectomy is complex and has yet to be fully elucidated but likely related to dysfunctional pyloric relaxation as well as disruption of gastric peristalsis. Oncologic resection of the esophagus necessitates dissection of the periesophageal lymphatics as well as division of the vagus nerves both of which likely contributed to delayed passage of food through the gastric conduit. For end-stage benign disease, Barrett’s with high grade dysplasia or early stage carcinoma, techniques for vagal sparing esophagectomy have been developed which may reduce the incidence of delayed gastric emptying . The impact of pyloric drainage procedures (pyloroplasty, pyloromyotomy or botox injection) during esophagectomy continues to be debated. Recent meta-analyses have not demonstrated significant improvement in gastric emptying studies after pyloric drainage procedures and a trend toward increased rates esophagitis and bile reflux .
Patients undergoing lung or combined heart/lung transplant are another subset of patients who are at increased risk of developing PSG. There are multiple proposed mechanisms for the development of PSG after lung transplant including viral infection and immunosuppression medication side effect, however vagal nerve injury due to dissection in the posterior mediastinum is considered the most likely mechanism. Multiple studies have demonstrated rates of post-operative delayed gastric emptying ranging from 25% to 50% depending on the procedure performed (single vs double lung or combined heart/lung transplant) and the timing of follow-up . Interestingly, in a study evaluating pre- and post-op gastric emptying studies following lung transplant, there was a 50% pre-operative prevalence of abnormal gastric emptying possibly related to their adjuvant therapies . PSG has important implications in the post-transplant patient due to the impact on immunosuppressant absorption and bioavailability. PSG has also been shown to be associated with an increased risk of developing post-operative respiratory failure, bronchiolitis obliterans syndrome and ultimately graft failure .
Once the diagnosis the gastroparesis has been confirmed, the initial therapy should be focused on correction of fluid and electrolytes imbalances and maintaining adequate nutrition. The patient should have a comprehensive medical evaluation and all potential underlying exacerbating conditions (diabetes, thyroid dysfunction, narcotic addiction, pathologic eating behaviors, etc.) should be addressed. In general, a conservative approach should be taken in the management of PSG as many of these patients will see improvement of their symptoms with time .
The mainstay of medical management of gastroparesis is dietary modification and prokinetic agents. Oral intake is preferable for nutrition and hydration, however in patients with insufficient oral intake a nasojejunal tube or surgical jejunostomy tube should be used. Parenteral nutrition should be used only when enteral feeding cannot be tolerated, such as in patients with whole gut dysmotility. Decompressive gastrostomy tubes, placed laparoscopically or endoscopically can be used for palliation in the case of refractory gastroparesis, however their routine use should be avoided in favor of interventions which aim to improve gastric emptying.
Patients should be encouraged to eat 4–5 small low-fat, low fiber meals per day as fat and fiber have been shown to slow gastric emptying. High calorie liquid may be helpful, as liquids often empty more readily than solids. Carbonated beverages should be avoided as they can exacerbate gastric distension and patients should abstain from alcohol and tobacco due to adverse impacts on gastric emptying .
Prokinetic agents should be used with caution due to their limited long-term efficacy and side effect profile. Metoclopramide is the only US FDA-approved medication for the treatment for gastroparesis. The FDA recommends treatment for no longer than 12 weeks unless the benefit of therapy outweigh the risks. Metoclopramide has been proven in randomized trials to improve gastric emptying, however none of those studies involved treatment regimens longer than 4 weeks . The side effects of the medication are rare but significant, including acute dystonia and tardive dyskinesia. (for more see chapter 24 “Prokinetics”).
Pyloroplasty has long been the mainstay of surgical treatment to improve gastric outflow. Pyloroplasty improves gastric emptying by relieving obstruction at the pylorus and increasing the cross-sectional area of the gastric outlet. This procedure can be done laparoscopically by creating a 5-centimeter longitudinal gastroduodenotomy and closing the defect transversely ( Fig. 19.1 ).