Keywords

Gastrectomy; Gastrojejunostomy; Postoperative; Gastroparesis; Delayed gastric emptying; Abdominal surgery; Roux-en-Y

Introduction

Gastroparesis is defined as a persistent heterogeneous defect in the gastric motility. Gastroparesis was an unfamiliar disability; it has become an increasingly reported disease in the past two to three decades [1]. It is characterized by the delayed gastric emptying after intake of solid food in the absence of a gastrointestinal obstruction. The symptoms can be mild or severe and they are mostly nausea, vomiting, epigastric pain, early satiety, fullness, anorexia, and/or weight loss [2]. Gastroparesis severely affects the patients’ nutrition, health, social interactions and even the duration of hospital stay [1]. The most common aetiologies include diabetes, post-surgical and idiopathic. Some studies suggest there are many other aetiologies for gastroparesis but in a large number of patients the cause is still unknown [3]. Gastric carcinoma is an internationally well-known disease. Gastrectomy has been established as the standardized management for gastric cancer [4,5]. An extended period of stasis followed by uncomplicated abdominal surgeries is not conventional. On routine, a post gastrectomy patient will have tolerated oral solid intake on postoperative day 10-14. However, in some cases the gastric motility function can be delayed. A situation as such is termed as postoperative gastroparesis syndrome (PGS) or delayed gastric emptying (DGE).

Postoperative Gastroparesis is defined as a complex disorder characterized by post-prandial nausea or vomiting, and gastric atony without the presence of a mechanical gastric outlet obstruction [3]. Postoperative Gastroparesis after gastric surgeries has been previously reported, with an incidence of approximately 5-25% [6]. It is also a frequent complication of pylorus-preserving pancreatoduodenectomy (PPPD), and the complication occurs in the early postoperative period in 20-50% of patients [7]. Abdominal surgeries are a common trigger for gastroparesis. Abdominal surgeries, especially partial gastrectomy and pylorus preserving pancreatoduodenectomy, account for 13% of the aetiologies, also, the third most common causes for gastroparesis [8]. The complication usually occurs when the patients start the solid diet intake or when there is a change in the form of food [9]. The feeling of nausea followed by constant vomiting, can build an impairing state of mind in the patient. Drug therapy is commonly known to be futile and occasionally gastric reoperations are nugatory [10]. Up till date the cause, as well as, the mechanism of postoperative gastroparesis remains unidentified and ambiguous [2]. During the past few years there has been a gradual increase in the incidence of the disease, seriously interfering with the postoperative recovery of surgical patients, with enormous mental, psychological and economic pressure on the patients. As the complication is not targeted to better treatment, it leads to a lengthened therapy, thus a slow recovery [11].

Some of the common parameters taken into considerations for assessing postoperative gastroparesis include the clinical condition of the patient, the comorbidities, diagnostic evaluation, duration of hospital stay, specific treatment, whether enteral or parenteral nutritional support was opted and interventional treatment [3]. The period of nasogastric drainage or the necessity of reinserting drainage tube, and the postsurgical day on which the patient could ingest oral solid food after the surgery are used to categorize the grade of stasis. According to current postoperative managements, the perioperative inserted nasogastric tube should be removed as soon as possible after surgery. Any nasogastric intubation lasting longer than three postoperative days should be considered as gastroparesis. Although, definitions from the early 1990s state that keeping the patient with a nasogastric tube for ten days postsurgical suggest gastroparesis, these definitions are nowadays redundant [12]. Therefore, postoperative gastroparesis should be considered on the need of a nasogastric tube longer than three days or the need for reinserting the nasogastric drainage tube on persistent vomiting beyond the third postsurgical day. The potential to be able to withstand solid diet is distinct goal in the management of patients after abdominal surgeries. Patient can be started on a liquid diet once the patient has passed out gas, which is usually on the first or second postoperative day, or after removal of the nasogastric drainage tube. As per clinical pathways, patients should be able to start a solid diet by a week after surgery. Therefore, the presence of gastroparesis is considered if patient is unable to digest a solid diet by postoperative day seven. According to the International Study Group of Pancreatic Surgery (ISGPS), postoperative gastroparesis can be divided into 3 grades, as such the mild form being grade A, moderate, grade B and the severe form classified as grade C, distinguished by their clinical impression [3]. For instance, postoperative gastroparesis Grade A does not usually involve change in management. It is commonly associated with just a few disturbances in reaction to intake of solid food, which might necessitate the reinsertion of nasogastric tube for a brief period. However, Grade B might involve treatment with prokinetic drugs, parenteral or enteral nutritional support and usually a prolonged reinsertion of the nasogastric tube is needed, while Grade C requires a major change in the management and treatment of the associated complications such as, pancreatic fistula or intra-abdominal abscesses. Consequently, additional diagnostic workup, radiological or surgical interventions are commonly essential [3].

Diagnostic Criteria

With the obvious signs of abdominal distension, vomiting, the daily amount of fluid in the NG tube, the need of reinsertion of NG tube, radiological examination plays an important role in confirming the diagnosis of postoperative gastroparesis [12]. It helps in confirming the presence or absences of mechanical obstruction, anastomosis leakages or whether there are any factors causing the symptoms in the patient. Gastric Scintigraphy remains by far the gold standard method for diagnosis of gastroparesis [13]. It is believed to be the most cost-effective, uncomplicated, easily accessible technique for confirmation of gastroparesis. Customarily, in non-surgical patients gastric emptying of solids is preferable to assess the severity of the condition. In postoperative patients, radioisotope liquid meal is opted due to the inability of tolerating solid meal [14]. It is crucial to bear in mind that patient with diabetes should always have their blood glucose level measured. Any presence of hyperglycaemia must not be disregarded; blood glucose level should be maintained at a level less that 275 mg/dL [15].

There are many other procedures that can be carried out for assessing gastroparesis, such as wireless motility capsules [16] and 13C Breath testing [17], which have proven to be less invasive than Gastric Scintigraphy [18,19]. Nevertheless, there is no evidence of their applications in diagnosing postoperative gastroparesis, which makes Gastric Scintigraphy the most recommended test to confirm the diagnosis of postoperative gastroparesis [20].

Management

The management of postoperative gastroparesis undoubtedly depends on the degree of severity, but given that all three grades have common symptoms, the initial treatment is standardly the same.

Diet

The American Gastroenterological Association suggests that patients presenting with vomiting should be cross-examined for other conditions like regurgitation or bulimia [21]. Postoperative patients who are experiencing nausea, vomiting or abdominal bloating after oral intake will tend to be anxious, depressed or even nervous [22]. Therefore, dietary manipulation is an important factor in managing postoperative gastroparesis [23]. Liquid nutrition is preferred since gastric emptying is maintained for liquids and diets low in fat or fibres. Also, hypertonic food is usually unfavourable in these conditions [13].

Prokinetic Medications

Prokinetic is an important factor for enhancing gastrointestinal motility. The common prokinetic drugs in clinical practice are metoclopramide, domperidone and erythromycin [24,25]. Metoclopramide is the only FDA approved drug for gastroparesis therapy. It acts by blocking the dopamine D2 and it stimulates 5-HT4 receptor in order to escalate the production of acetylcholine [13,15,26]. Nonetheless, metoclopramide can also have some disadvantages. Patients suffering from postoperative gastroparesis are vulnerable to depression. Using Metoclopramide can worsen depression or even lead to other conditions like Tardive dyskinesia, Akathisia or even Parkinsonism, due to its BBB (blood brain barrier) crossing property [27,28].

Domperidone is opted when there is effect of metoclopramide on the symptoms or patients present with side effects of metoclopramide. Despite the fact that the domperidone is as efficacious as metoclopramide, there are not enough clinical trials thus limiting its use [29]. Domperidone can present with cardiac arrhythmias or even hyperprolactinemia.

Erythromycin is a motilin agonist which improves postoperative gastric emptying when used in small doses [30-32]. Erythromycin is chosen for patients who are unable to show improvement with metoclopramide and domperidone. Conversely, erythromycin cannot be used for more than four weeks, due to a decrease in its effect. An increase in dose can lead to abdominal pain or tachyphylaxis [33-36].

Surgical Treatment

Surgery has not been established the treatment of choice in postoperative gastroparesis [23], probably because it would mean making the patient undergoing surgery again. A metaanalysis has shown that there are not enough evidence supporting surgery as the treatment for gastroparesis [37]. However, if the symptoms aggravate or do not alleviate, surgery can be an option [38-41]. The most effective surgery for treating postoperative gastroparesis can be total gastrectomy followed by a Roux-en-Y reconstruction [13,41,42]. Roux-en-Y has furthermore shown to be accompanied by a postoperative complication of intussusception. Some studies suggest that total gastrectomy with Roux-en-Y esophagojejunostomy should be opted to prevent postoperative complications [43-45].

Traditional Chinese Medicine

There are many cases where patients do not respond to prokinetic medication for gastroparesis, and some may consider surgical treatment as expensive. In these particular cases, the patient can opt for Traditional Chinese Medicine therapy to treat the symptoms of gastroparesis. In cases of nausea and vomiting, the Xiao-Banxia-Tang can be prescribed, while ZhiZhu Wan is recommended for patients who experience bloating [15]. It should be noted that in TCM the treatment program for gastroparesis is to be chosen based on the presenting symptoms of the patient. The clinical guidelines for management of gastroparesis suggests acupuncture as a surrogate therapy, owing to the fact that it has shown to improve the rates of gastric emptying and it has shown a decrease in the presenting symptoms [46].

Gastric Electric Stimulation

The device for gastric electric stimulation was approved by the FDA for treatment of gastroparesis but initially was excluded for treatment of diabetic and idiopathic gastroparesis [47]. Advancing studies have shown this form of management is positive for both types [46]. Despite the fact that gastric electric stimulation has shown to have effects on gastrointestinal symptoms within 72 hours of initiating of treatment, which undeniable substantiates the rapid efficacy of gastric electric stimulation, there are not enough evidence to support this choice of treatment in postoperative gastroparesis [48]. The clinical guideline for treatment of gastroparesis also states that there are no guidelines for selecting patients to adapt this management [46,49].

Botulinum Toxin Injection

Botulinum Toxin Injection is known as to have a potential inhibitory action on the neuromuscular transmissions [41]. Few studies have shown to have an improvement on the pylorospasm symptom in gastroparesis [50,51], however the clinical guideline suggests that it should not be opted as a treatment for this complication [46].

Proposed Causes and Discussion

There are multiple proposed causes of gastroparesis among which 36% are idiopathic cases, diabetes forming 29% of them and 13% are postoperative cases [13]. Gastroparesis is considered to be a complicated state caused by a disorder of the gastric motility, due to the incoordination of the enteric neurons or the smooth muscle cells or even the autonomic nervous system, together with a reduced amount of pacemaker cells also known as the interstitial cells of Cajal [52-56]. It has been suggested postoperative gastroparesis can occur due to ischemia [57,58] or a reduced in gastric motility. Multiple comorbidities such as diabetes mellitus can be one of the factors leading to postoperative gastroparesis [8]. Some studies suggest that postoperative gastroparesis might be a result of the removal of the moitilin receptor during the surgery which leads to a lowered stimulation of the receptor [10]. The surgical method chosen for gastric cancer has a great impact on postoperative gastroparesis. It has been suggested that it can occur due to the removal of or a damage to the vagus nerve [58,59]. One of the studies proposes a retro-colic anastomosis as one of the factors leading to gastroparesis [50]. It was suggested that it could due to the presence of additional resistance to the gastric contents after a retro-colon gastrointestinal reconstruction.

Gastrectomy followed by one of three reconstruction techniques, Billroth I, Billroth II or Roux-en-Y gastrojejunostomy, is the standardized method. The majority of studies suggest that Roux-en-Y reconstruction has previously been proved to be the better reconstruction method than Billroth reconstructions after gastrectomy [60-63]. Nonetheless, it has been reported that Roux-en-Y reconstruction surgeries are commonly associated with Roux-en-Y stasis syndrome which is influenced easily by the length of the Roux Limb [64]. It has been suggested that incoordination of the efferent Limb might itself lead to stasis. It is believed that the idea length would be 25cm in order to prevent stasis [65]. Many patients undergoing distal gastrectomy with vagotomy or gastric bypass for obese patients followed by Rouxen- Y anastomosis reported to have suffered from postoperative gastroparesis [20,66-68]. Fewer studies suggest that a Billroth reconstruction method could also contribute to postoperative gastroparesis [64,68,69], contraindicating the other studies which state abdominal surgeries followed by a Billroth II surgery result in a lesser rate of postoperative gastroparesis [70]. It is assumed that the combination of the above-mentioned procedures predisposes to slow emptying, because an extrinsic denervation decreases the ability of the stomach to digest solid, which may result in the formation of bezoars.

Conclusion

Postoperative causes represent the third most common aetiology of gastroparesis. Gastric Scintigraphy, the gold standard method, along with a nasogastric drainage and a tolerance to solid food are the main factors considered when diagnosing and grading postoperative gastroparesis. While there are no preferable method to prevent gastroparesis, the studies reviewed have suggested prokinetic as drug therapy. Re-surgical intervention, gastric electric stimulation and botulinum toxin injection can be considered as a management. TCM proves to be a satisfactory choice for treating the symptoms of postoperative gastroparesis. It has been reported in the past that most cases of postoperative gastroparesis were a result of previous thoracic or gastric surgeries with unintentional injury to vagus nerve or vagotomy in combination with gastric drainage for cases of peptic ulcer diseases. Vagal injury, both permanent or reversible, is a common complication after fundoplication or even sclerotherapy for management of achalasia. Various studies have suggested that other than vagotomy, a reduced amount in pacemaker cells can also account for causes of postoperative gastroparesis. It is also believed that an inadequate blood supply of the anastomosis, inadequate nutritional supply or a delay in starting oral intake could also be relevant factors leading to postoperative gastroparesis. Postoperative gastroparesis remains the most commonly seen complication after distal gastrectomy followed by Roux-en-Y reconstruction method. However, there is no valid evidence for the mechanism which makes the exact cause of postoperative gastroparesis remain unclear.

Declarations

Funding: None

Conflict of interest: None declared

Ethical approval: Not required

References

1. Wang YR, Fisher RS, Parkman HP (2008) Gastroparesis-related hospitalizations in the United States: trends, characteristics, and outcomes, 1995–2004. Am J Gastroenterol 103: 313-322.
2. Dong K, Yu XJ, Li B, Wen EG, Xiong W, et al. (2006) Advances in mechanisms of postsurgical gastroparesis syndrome and its diagnosis and treatment. Chin J Dig Dis 7:76-82.
3. Wente MN, Bassi C, Dervenis C, Fingerhut A, Gouma DJ, et al. (2007) Delayed gastric emptying (DGE) after pancreatic surgery: A suggested definition by the International Study Group of Pancreatic Surgery (ISGPS). Surgery 142:761-768.
4. Swan R, Miner TJ (2006) Current role of surgical therapy in gastric cancer. World J Gastroenterol 12:372-379.
5. Xiong JJ, Altaf K, Javed MA, Nunes QM, Huang W, et al. (2013) Roux-en-Y versus Billroth I reconstruction after distal gastrectomy for gastric cancer: a meta-analysis. World J Gastroenterol 19:1124-1134.
6. Hinder RA, Esser J, DeMeester TR (1988) Management of gastric emptying disorders following the Roux-en-Y procedure. Surgery 104:765–772.
7. Takayama Y, Kaneoka Y, Maeda A, Fukami Y, Onoe S (2017) Extracorporeal Hand-Sewn Anastomosis Through a Minilaparotomy in Laparoscopic Distal Gastrectomy. J Laparoendosc Adv Surg Tech A 27: 726-732.
8. Tang DM, Friedenberg FK (2011) Gastroparesis: Approach, diagnostic evaluation, and management. Dis Mon 57:74-101.
9. Akizuki E, Kimura Y, Nobuoka T, Imamura M, Nagayama M, et al. (2009) Reconsideration of postoperative oral intake tolerance after pancreaticoduodenectomy: prospective consecutive analysis of delayed gastric emptying according to the ISGPS definition and the amount of dietary intake. Ann Surg 249:986-994.
10. Dong K, Li B, Guan QL, Huang T (2004) Analysis of multiple factors of postsurgical gastroparesis syndrome after pancreaticoduodenectomy and cryotherapy for pancreatic cancer. World J Gastroenterol 10:2434-2438.
11. Meng H, Zhou D, Jiang X, Ding W, Lu L (2013) Incidence and risk factors for postsurgical gastroparesis syndrome after laparoscopic and open radical gastrectomy. World J Surg Oncol 11:144.
12. Strömmer L, Räty S, Hennig R, Adrian TE, Friess H, et al. (2005) Delayed gastric emptying and intestinal hormones following pancreatoduodenectomy. Pancreatology 5:537-544.
13. Waseem S, Moshiree B, Draganov PV (2009) Gastroparesis: Current diagnostic challenges and management considerations. World J Gastroenterol 15:25-37.
14. Le Roux PY, Bouchet F, Querellou S, Vervueren L, Lacoeuille F, et al. (2011) American consensus recommendations for gastric scintigraphy: curve fitting with only a few points remains an easy and accurate method to obtain reliable and reproducible gastric emptying estimates. Nucl Med Commun 32:30-36.
15. Li JL, Li M, Pang B, Zhou Q, Tian JX, et al. (2014) Combination of symptoms, syndrome and disease: Treatment of refractory diabetic gastroparesis. World J Gastroenterol 20:8674-8680.
16. Lee YY, Erdogan A, Rao SSC (2014) How to Assess Regional and Whole Gut Transit Time With Wireless Motility Capsule. J Neurogastroenterol Motil 20:265-270.
17. Ghoos YF, Maes BD, Geypens BJ, Mys G, Hiele MI, et al. (1993) Measurement of gastric emptying rate of solids by means of a carbon-labeledoctanoic acid breath test. Gastroenterology 104:1640-1647.
18. Braden B, Adams S, Duan LP, Orth KH, Maul FD, et al. (1995) The [13C] acetate breath test accurately reflects gastric emptying of liquids in both liquid and semisolid test meals. Gastroenterology 108:1048-1055.
19. Camilleri M, Hasler WL, Parkman HP, Quigley EM, Soffer E (1998) Measurement of gastrointestinal motility in the GI laboratory. Gastroenterology 115:747-762.
20. Feinle C, Kunz P, Boesiger P, Fried M, Schwizer W (1999) Scintigraphic validation of a magnetic resonance imaging method to study gastric emptying of a solid meal in humans. Gut 44: 106-111.
21. Parkman HP, Hasler WL, Fisher RS (2004) American Gastroenterological Association medical position statement: diagnosis and treatment of gastroparesis. Gastroenterology 127:1589-1591.
22. Kim YH (2012) Management and prevention of delayed gastric emptying after pancreaticoduodenectomy. Korean J HepatobiliaryPancreatSurg16:1-6.
23. Davis JL, Ripley RT (2017) Postgastrectomysyndromes and nutritional considerations following gastric surgery. Surg Clin North Am 97:277-293.
24. Lee AL, Kim CB (2012) The effect of erythromycin on gastrointestinal motility in subtotal gastrectomized patients. J Korean Surg Soc 82:149-155.
25. Donovan OD, Bisset FC, Jones K, Horowitz M (2003) Idiopathic and diabetic gastroparesis. Curr Treat Options Gastroenterol 6:299-309.
26. Malagelada JR, Rees WD, Mazzotta LJ, Go VL (1980) Gastric motor abnormalities in diabetic and postvagotomygastroparesis: effect of metoclopramide andbethanechol. Gastroenterology 78:286-293.
27. Rao AS, Camilleri M (2010) Review article: Metoclopramide and tardive dyskinesia. Aliment Pharmacol Ther31:11-19.
28. Ganzini L, Casey DE, Hoffman WF, McCall AL (1993) The prevalence of metoclopramide-induced tardive dyskinesia and acute extrapyramidal movement disorders. Arch Intern Med 153:1469-1475.
29. Sugumar A, Singh A, Pasricha PJ (2008) A systematic review of the efficacy of domperidone for the treatment of diabetic gastroparesis. Clin Gastroenterol Hepato l6:726-733.
30. Matsunaga H, Tanaka M, Takahata S, Ogawa Y, Naritomi G, et al. (2000) Manometric evidence of improved early gastric stasis by erythromycin after pylorus-preserving pancreatoduodenectomy. World J Surg 24:1236-1241.
31. Ohwada S, Satoh Y, Kawate S, Yamada T, Kawamura O, et al. (2001) Low-dose erythromycin reduces delayed gastric emptying and improves gastric motility after Billroth I pylorus-preserving pancreaticoduodenectomy. Ann Surg 234:668-674.
32. JadcherlaSR, Berseth CL (2002) Effect of erythromycin on gastroduodenal contractile activity in developing neonates. J Pediatr Gastroenterol Nutr 34:16-22.
33. Torra RC, Casadevall EG, Cots AE, Fernández JL, VidaurAF (1994) Usefulness of erythromycin in severe postoperative gastroparesis. Rev Esp Enferm Dig 85:38-40.
34. Camilleri M (1994) Appraisal of medium and long-term treatment of gastroparesis and chronic intestinal dysmotility. Am J Gastroenterol 89:1769-1774.
35. Ramirez B, Eaker EY, Drane WE, Hocking MP, Sninsky CA (1994) Erythromycin enhances gastric emptying in patients with gastroparesis after vagotomy and antrectomy. Dig Dis Sci 39:2295-2300.
36. Kendall BJ, Chakravarti A, Kendall E, Soykan I, McCallum RW (1997) The effect of intravenous erythromycin on solid meal gastric emptying in patients with chronic symptomatic post-vagotomy-antrectomygastroparesis. Aliment Pharmacol Ther 11:381-385.
37. Jones MP, Maganti K (2003) A systematic review of surgical therapy for gastroparesis. Am J Gastroenterol 98:2122-2129.
38. Watkins PJ, Buxton-Thomas MS, Howard ER (2003) Long-term outcome after gastrectomy for intractable diabetic gastroparesis. Diabet Med 20:58-63.
39. Speicher JE, Thirlby RC, Burggraaf J, Kelly C, Levasseur S (2009) Results of completion gastrectomies in 44 patients with postsurgical gastric atony. J Gastrointest Surg 13:874-880.
40. Clark CJ, Sarr MG, Arora AS, Nichols FC, Reid-Lombardo KM (2011) Does gastric resection have a role in the management of severe postfundoplication gastric dysfunction? World J Surg 35:2045-2050.
41. Radaelli F, Paggi S, Terreni N, Toldi A, Terruzzi V (2010) Acute reversible gastroparesis and megaduodenum after botulinum toxin injection for achalasia Gastrointest Endosc 71:1326-1327.
42. EckhauserFE, Knol JA, Raper SA, Guice KS (1988) Completion gastrectomy for postsurgical gastroparesis syndrome. Preliminary results with 15 patients. Ann Surg 208:345-353.
43. McCallum RW, Polepalle SC, Schirmer B (1991) Completion gastrectomy for refractory gastroparesis following surgery for peptic ulcer disease. Long-term follow-up with subjective and objective parameters. Dig Dis Sci 36:1556-1561.
44. Ducrotté P (1992) Postoperative gastroparesis after partial gastrectomy for ulcer: Should total gastrectomy be preferred? Gastroenterol Clin Bio l16:379.
45. Farahmand M, Sheppard BC, Deveney CW, Deveney KE, Crass RA (1997) Long-term outcome of completion gastrectomy for nonmalignant disease. J Gastrointest Surg 1:182-187.
46. Camilleri M, Parkman HP, Shafi MA, Abell TL, Gerson L (2013) Clinical Guideline: Management of Gastroparesis. Am J Gastroenterol 108:18-38.
47. Stanciu GO (2001) Gastroparesis and its management. Rev Med ChirSoc Med Nat Iasi 105:451-456.
48. Abell T, Lou J, Tabbaa M, Batista O, Malinowski S, et al. (2003) Gastric electrical stimulation for gastroparesis improves nutritional parameters at short, intermediate, and long-term follow-up. J Parenter Enteral Nutr27:277-281.
49. Lin Z, Forster J, Sarosiek I, McCallum RW (2003) Treatment of gastroparesis with electrical stimulation. Dig Dis Sci48:837-848.
50. Friedenberg FK, Palit A, Parkman HP, Hanlon A, Nelson DB (2008) Botulinum toxin A for the treatment of delayed gastric emptying. Am J Gastroenterol 103:416-423.
51. Friedenberg FK, Parkman HP (2006) Delayed gastric emptying: whom to test, how to test, and what to do. Curr Treat Options Gastroenterol 9:295-304.
52. Samin KA, Alam I, Riaz S, Alam S, Baxter JN (2006) Gastro-ileal stenosis and gastroparesis after a biliopancreatic diversion. Obes Surg 16:1243-1245.
53. Salameh JR, Schmieg RE, Runnels JM, Abell TL (2007) Refractory gastroparesis after Roux-en-Y gastric bypass: surgical treatment with implantable pacemaker. J Gastrointest Surg 11:1669-1672.
54. Ma IT, Madura JA (2015) Gastrointestinalcomplications after bariatric surgery. GastroenterolHepatol (N Y) 11:526-535.
55. Ordög T, Takayama I, Cheung WK, Ward SM, Sanders KM (2004) Remodeling of networks of interstitial cells of Cajal in a murine model of diabetic gastroparesis. Diabetes 49:1731-1739.
56. Zarate N, Mearin F, Wang XY, Hewlett B, Huizinga JD, et al. (2003) Severe idiopathic gastroparesis due to neuronal and interstitial cells of Cajal degeneration: Pathological findings and management. Gut 52:966-970.
57. Bu XM, Xu J, Dai XW, Ma K, Yang FQ, et al. (2006) Is delayed gastric emptying so terrible after pylorus-preserving pancreaticoduodenectomy? Prevention and management. World J Gastroenterol 12: 6382–6385.
58. Kim DK, Hindenburg AA, Sharma SK, Suk CH, Gress FG, et al. (2005) Is pylorospasm a cause of delayed gastric emptying after pylorus-preserving pancreaticoduodenectomy? Ann Surg Oncol 12:222-227.
59. Tani M, Terasawa H, Kawai M, Ina S, Hirono S, et al. (2006) Improvement of delayed gastric emptying in pylorus-preserving pancreaticoduodenectomy: Results of a prospective, randomized, controlled trial. Ann Surg 243:316-320.
60. Csendes A, Burgos AM, Smok G, Burdiles P, Braghetto I, et al. (2009) Latest results (12-21 years) of a prospective randomized study comparing Billroth II and Roux-en-Y anastomosis after a partial gastrectomy plus vagotomy in patients with duodenal ulcers. Ann Surg 249:189-194.
61. Hoya Y, Mitsumori N, Yanaga K (2009) The advantages and disadvantages of a Roux-en-Y reconstruction after a distal gastrectomyfor gastric cancer.  Surg Today 39:647-651
62. Hornbuckle K, Barnett J (2000) The diagnosis and work-up of the patient with gastroparesis. J Clin Gastroenterol 30:117-124.
63. Ceriani V, Lodi T, Porta A, Roncaglia O, Osio C, et al. (2011) Roux-en-Y reconstruction at greater curvature in biliopancreatic diversion: effects on early postoperative functional recovery. Obes Surg 21:1188-1193.
64. Otsuka R, Natsume T, Maruyama T, Tanaka H, Matsuzaki H (2015) Antecolic reconstruction is a predictor of the occurrence of roux stasis syndrome after distal gastrectomy. J Gastrointest Surg 19:821-824.
65. Park YC, Kim SW, Jang JY, Ahn YJ, Park YH (2003) Factors influencing delayed gastric emptying after pylorus-preserving pancreatoduodenectomy. J Am Coll Surg196:859-865.
66. Hirao M, Fujitani K, Tsujinaka T (2005) Delayed gastric emptying after distal gastrectomy for gastric cancer. Hepatogastroenterology 52:305-309.
67. Glowka TR, Webler M, Matthaei H, Schäfer N, Schmitz V, et al. (2017) Delayed gastric emptying following pancreatoduodenectomy with alimentary reconstruction according to Roux-en-Y or Billroth-II. BMC Surg 17:24.
68. Zhang MJ, Zhang GL, Yuan WB, Gao C (2014) Analysis of possible clinical risk factors contributing to postsurgical gastroparesissyndrom (PGS) after subtotal gastrectomy. Hepatogastroenterology 61:849-852.
69. Paik HJ, Choi CI, Kim DH, Jeon TY, Kim DH, et al. (2014) Risk factors for delayed gastric emptying caused by anastomosis edema after subtotal gastrectomy for gastric cancer. Hepatogastroenterology 61:1794-1800.
70. Lytras D, Paraskevas KI, Avgerinos C, Manes C, Touloumis Z, et al. (2007) Therapeutic strategies for the management of delayed gastric emptying after pancreatic resection. Langenbecks Arch Surg 392:1-12.