528400 research-article2014
PMJ0010.1177/0269216314528400Palliative Medicine X(X)Franco and Koulaeva
Case Report
Nasogastric tube insertion followed by intravenous and oral erythromycin in refractory nausea and vomiting secondary to paraneoplastic gastroparesis: A case report
Palliative Medicine 2014, Vol. 28(7) 986–989 © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0269216314528400 pmj.sagepub.com
Michael Franco1,2 and Eugenia Koulaeva3
Abstract Background: Gastroparesis is an under-recognised cause of refractory nausea and vomiting in patients with malignancy. The most common aetiologies are paraneoplastic and postsurgical dysmotility. There are little data on the efficacy of treatment to direct the management of patients with this symptom. We present a case and brief summary of current literature. Case presentation: We present the case of a 72-year-old patient with metastatic neuroendocrine carcinoma of the pancreas with dehydration and renal impairment secondary to nausea and vomiting. Replacement of duodenal stent, gastroscopy, endoscopic retrograde cholangiopancreatogram and gastric motility studies revealed gastroparesis rather than mechanical obstruction. Case management: The patient was transferred to an inpatient palliative care unit for symptom management where a nasogastric tube was inserted, followed by intravenous erythromycin with excellent improvement in symptoms and oral intake. He was switched to oral erythromycin with ongoing effect. Case outcome: With stabilisation of symptoms and renal function, the patient was able to be discharged with maintenance of good symptomatic control. Conclusions: Further research is needed into the management of gastroparesis in palliative care patients. In particular, we suggest that initial drainage with a nasogastric tube followed by a course of erythromycin warrants further study. Keywords Gastroparesis, erythromycin, palliative medicine, nausea, vomiting
What is already known about the topic? • There is little evidence around the best treatment of gastroparesis in palliative care patients. • T here are data for the efficacy of erythromycin in the treatment of diabetic gastroparesis, however, little literature exists on malignancy-related gastroparesis, in particular paraneosplastic gastroparesis. • Paraneoplastic syndromes such as gastroparesis are common in patients with neuroendocrine tumours, especially small cell lung carcinoma and pancreatic neuroendocrine carcinoma. • Nasogastric tube (NGT) insertion has not been studied in the management of gastroparesis in palliative care settings. What this paper adds? • Palliative care units can successfully provide invasive management, such as NGT insertion, for symptom control. • NGT insertion combined with erythromycin can have a positive impact on symptoms relating to paraneoplastic gastroparesis. • Oral erythromycin following initial intravenous (IV) erythromycin can continue to be effective in paraneoplastic gastroparesis.
1Palliative
and Supportive Care Unit, Monash Medical Centre Clayton, Monash Health, Clayton, VIC, Australia 2Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, VIC, Australia 3Monash Health, Clayton, VIC, Australia
Corresponding author: Michael Franco, Palliative and Supportive Care Unit, McCulloch House, Monash Medical Centre Clayton, Monash Health, 246 Clayton Rd, Clayton, VIC 3168, Australia. Email: [email protected]
987
Franco and Koulaeva Implications for practice, theory or policy
• T here is need for research in the use of erythromycin and NGT insertion in gastroparesis, especially in the palliative patient population. • The use of erythromycin may be effective in malignancy-associated gastroparesis. • This article also further supports the use of novel management strategies in palliative care units to alleviate symptoms, potentially allowing patients to be discharged home.
Background Nausea and vomiting are two of the most common symptoms that require management in a typical palliative care patient population. While the aetiology of nausea and vomiting is often easy to discern, there is a subset of this patient population in which the causes are less clear and thus management becomes a significant challenge. One of the less common but still under-recognised causes of nausea and vomiting is gastroparesis.1 In palliative medicine, the majority of cases of gastroparesis seen will be in patients with metastatic malignancy. However, with its ever-increasing prevalence, greater numbers of patients with gastroparesis secondary to the autonomic neuropathy of type II diabetes mellitus are likely to be incidentally encountered. There are numerous aetiologies of gastroparesis relevant to patients with metastatic malignancy, including paraneoplastic syndromes, as a side effect from chemo- or radiotherapy and infiltration of the coeliac plexus. Particular primary malignancies are most associated with paraneoplastic gastroparesis. The most common are tumours of neuroendocrine origin, for example, pancreatic cancer, small cell lung cancer and carcinoid tumours.2 The pathogenesis in these cancers appears to be related to the prevalence of anti-Hu antibodies, which mediate autonomic dysfunction that leads to gastroparesis in these patients. Their prevalence is highest in small cell lung cancer, where one case series of 196 patients found 16% to be anti-Hu antibody positive.3 The treatment of gastroparesis of all causes is often challenging, and current literature is limited to studies of prokinetic agents, botulinum toxin injection and, in severe refractory cases, surgery and gastro-electrical stimulation. While there are several small trials and case studies regarding erythromycin in diabetic and idiopathic gastroparesis,4,5 there has only been a single case study published in palliative medicine literature.6 The literature on treatment of paraneoplastic gastroparesis is even more limited, and currently, only a single review article detailing general recommendations drawn from non-malignant literature has been published.7 At present, there are no published literature on the use of erythromycin in malignancy-induced gastroparesis or the combination of nasogastric tube (NGT) and erythromycin in gastroparesis of any cause.
We report a case of a patient with a pancreatic neuroendocrine cancer who was successfully treated with NGT insertion, followed by intravenous (IV) and then oral erythromycin.
Case presentation A 72 year-old man with a neuroendocrine pancreatic tumour requiring multiple biliary and duodenal stents was referred to our palliative care unit (PCU) by an acute gastroenterology unit for symptom management. On admission to gastroenterology, the patient presented with a month-long history of progressive nausea and vomiting, weight loss and lethargy. Prior to this, the patient had recently moved to a residential care facility and was ambulating independently. Initial endoscopy revealed malignant infiltration of the duodenal stent, which was successfully replaced; however, the severe nausea and vomiting continued. An ensuing barium swallow revealed minimal contrast in the first part of duodenum, retrograde flow into the biliary tree and no contrast into third part of the duodenum. Repeat endoscopy a day later showed a dilated stomach, no appreciable biliary obstruction and completely patent duodenal and biliary stents with contrast freely flowing into the distal duodenum. Thus, the final diagnosis from the gastroenterology unit was of paraneoplastic gastroparesis for which metoclopramide 60 mg, haloperidol 1.5 mg via continuous subcutaneous infusion (CSCI) and domperidone 20 mg TDS orally was commenced in an attempt to improve gastric emptying and relieve symptoms. On admission to PCU, the patient was still intolerant of any oral intake, had abdominal pain and reduced bowel motions and persistent vomiting, each of large volume. On examination, there was epigastric tenderness and hyperactive bowel sounds.
Case management After admission to the PCU, the patient was very reluctant to ambulate as he felt the nausea and vomiting were directly related to mobility. At this point, a NGT was offered. Following NGT insertion, there was initial improvement with cessation of vomiting, and the patient was subsequently able to ambulate around the ward. However, symptoms recurred 2 days later.
988
Palliative Medicine 28(7)
Given that the patient’s primary goal was to return back to his residential facility, he was tolerating oral intake, other symptoms had resolved and he was ambulant, the patient was discharged after a 21-day stay in the PCU. The patient’s symptoms remained well controlled with no change in medication until his death later that month.
given intravenously. While it was previously thought that this action directly stimulates peristalsis, more recently, it has been suggested that the major action of motilin and motilin agonists at therapeutic doses is to facilitate cholinergic mediation of gastrointestinal smooth muscle.11 To date, studies of erythromycin have been limited by small patient numbers, not using validated symptom assessment scores or having symptom control as a primary endpoint.12 Additionally, there have been no specific studies of its use in palliative patients or in gastroparesis of a paraneoplastic or direct malignant cause. Multiple pharmacokinetic studies have shown erythromycin to be more effective than metoclopramide in stimulation of gastric emptying as measured by residual gastric volume and intestinal drug absorption after administration.4 Additionally, other studies of gastroparetic patients show correlation between these objective measures and patient symptoms; thus, it is reasonable to postulate that erythromycin may be the more effective treatment.1 There is little evidence regarding the use of NGT drainage and decompression in patients with gastroparesis or regarding the use of NGTs in PCUs. Current literature is limited to the exploratory use of venting enterostomy in pseudo-obstruction in two retrospective case series (which included paediatric patients) and concluded that enterostomy can improve symptoms and reduce hospitalisation in selected patients.13
Discussion
Conclusion
The patient discussed in this case is typical of patients with gastroparesis of paraneoplastic aetiology. Neuroendocrine tumours have higher rates of paraneoplastic syndromes than other malignancies and make this an important differential diagnosis for the patient’s refractory nausea and vomiting.2 The data for treatment of these syndromes are limited. As with other paraneoplastic syndromes, improvement of symptoms may be seen if the underlying cancer is able to be treated.8 Clearly, this may not be a viable option once a patient has been referred for palliative care input, and thus, other symptomatic treatments are required. The best data exist for pharmacotherapy with the prokinetic medications metoclopramide or erythromycin.1 Metoclopramide’s facilitation of gastric emptying is via agonism of 5-HT4 receptors on enteric neurones that promote gastric emptying by enhancing antral contractions.9 The role of metoclopramide’s D2 receptor activity appears to relate more to its antiemetic function rather than directly promote prokinesis.10 Current literature in malignancyassociated gastroparesis is limited to one prospective case series of 10 patients which showed subjective and objective clinical benefit with administration of metoclopramide.4 Erythromycin is a motilin agonist that acts indirectly on gastric smooth muscle and is particularly potent when
Paraneoplastic gastroparesis is relatively common, underrecognised and can cause significant morbidity and negative impact on quality of life in patients with small cell and other neuroendocrine carcinomas. In many palliative patients, treatment of the underlying malignancy is no longer possible, and hence, a symptom-based approach is required. In the case described, an approach of NGT decompression and drainage of stomach contents followed by IV and oral erythromycin was effective in improving symptoms. Further studies into the prevalence and best management of paraneoplastic gastroparesis – in particular the use of NGT insertion and erythromycin – are warranted.
Given the symptom recurrence, the motilin agonist erythromycin was commenced. Initially, erythromycin was administered intravenously at 180 mg TDS (3 mg/kg, patient weight ~60 kg). The NGT became dislodged the next day, and it was decided to trial continuing the erythromycin without NGT reinsertion. Two days following commencement of erythromycin, the patient had significant symptom resolution. He was painfree, had moved his bowels, was tolerating a soft diet with no associated nausea or vomiting and was ambulating independently. IV erythromycin was continued for a total of 5 days. At this point, the erythromycin was changed to an oral maintenance dose of 125 mg oral TDS, and metoclopramide was also changed to oral administration the same day. Following the change to the oral route of administration, the patient had several episodes of nausea and vomiting; however, these settled with an increase in dose of metoclopramide to 20 mg orally QID.
Case outcome
Acknowledgements The patient gave written informed consent. We would like to acknowledge his contribution and are indebted to him for allowing this report to be written.
Declaration of conflicting interests The authors declare that there is no conflict of interest.
Funding This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.
Franco and Koulaeva References 1. Horowitz M, Su YC, Rayner CK, et al. Gastroparesis: prevalence, clinical significance and treatment. Can J Gastroenterol 2001; 15: 805–813. 2. Nguyen-tat M, Pohl J, Gunter E, et al. Severe paraneoplastic gastroparesis associated with anti-Hu antibodies preceding the manifestation of small-cell lung cancer. Z Gastroenterol 2008; 46: 274–278. 3. Graus F, Dalmou J, Rene R, et al. Anti-Hu antibodies in patients with small-cell lung cancer: association with complete response to therapy and improved survival. J Clin Oncol 1997; 15: 2866–2872. 4. Janssens J, Peeters TL, Vantrappen G, et al. Improvement of gastric emptying in diabetic gastroparesis by erythromycin. Preliminary studies. N Engl J Med 1990; 322: 1028–1031. 5. Janssen P, Harris MS, Jones M, et al. The relation between symptom improvement and gastric emptying in the treatment of diabetic and idiopathic gastroparesis. Am J Gastroenterol 2013; 108: 1382–1391. 6. Hunter A, Regnard C and Armstrong C. The use of longterm, low-dose erythromycin in treating persistent gastric stasis. J Pain Symptom Manage 2005; 29: 430–433.
989 7. Donthireddy KR, Ailawadhi S, Nasser E, et al. Malignant gastroparesis: pathogenesis and management of an underrecognized disorder. J Support Oncol 2007; 5: 355–363. 8. Caras S, Laurie S, Cronk W, et al. Case report: pancreatic cancer presenting with paraneoplastic gastroparesis. Am J Med Sci 1996; 312: 34–36. 9. Sanger GJ. Translating 5-HT4 receptor pharmacology. Neurogastroenterol Motil 2009; 21: 1235–1238. 10. Sanger GJ, Broad J and Andrews PL. The relationship between gastric motility and nausea: gastric prokinetic agents as treatments. Eur J Pharmacol 2013; 715: 10–14. 11. Broad J, Mukherjee S, Samadi M, et al. Regional- and agonist-dependent facilitation of human neurogastrointestinal functions by motilin receptor agonists. Br J Pharmacol 2012; 167: 763–774. 12. Maganti K, Onyemere K and Jones MP. Oral erythromycin and symptomatic relief of gastroparesis: a systematic review. Am J Gastroenterol 2003; 98: 259–263. 13. Murr MM, Sarr MG and Camilleri M. The surgeon’s role in the treatment of chronic intestinal pseudoobstruction. Am J Gastroenterol 1995; 90: 2147–2151.
PMJ0010.1177/0269216314528400Palliative Medicine X(X)Franco and Koulaeva
Case Report
Nasogastric tube insertion followed by intravenous and oral erythromycin in refractory nausea and vomiting secondary to paraneoplastic gastroparesis: A case report
Palliative Medicine 2014, Vol. 28(7) 986–989 © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0269216314528400 pmj.sagepub.com
Michael Franco1,2 and Eugenia Koulaeva3
Abstract Background: Gastroparesis is an under-recognised cause of refractory nausea and vomiting in patients with malignancy. The most common aetiologies are paraneoplastic and postsurgical dysmotility. There are little data on the efficacy of treatment to direct the management of patients with this symptom. We present a case and brief summary of current literature. Case presentation: We present the case of a 72-year-old patient with metastatic neuroendocrine carcinoma of the pancreas with dehydration and renal impairment secondary to nausea and vomiting. Replacement of duodenal stent, gastroscopy, endoscopic retrograde cholangiopancreatogram and gastric motility studies revealed gastroparesis rather than mechanical obstruction. Case management: The patient was transferred to an inpatient palliative care unit for symptom management where a nasogastric tube was inserted, followed by intravenous erythromycin with excellent improvement in symptoms and oral intake. He was switched to oral erythromycin with ongoing effect. Case outcome: With stabilisation of symptoms and renal function, the patient was able to be discharged with maintenance of good symptomatic control. Conclusions: Further research is needed into the management of gastroparesis in palliative care patients. In particular, we suggest that initial drainage with a nasogastric tube followed by a course of erythromycin warrants further study. Keywords Gastroparesis, erythromycin, palliative medicine, nausea, vomiting
What is already known about the topic? • There is little evidence around the best treatment of gastroparesis in palliative care patients. • T here are data for the efficacy of erythromycin in the treatment of diabetic gastroparesis, however, little literature exists on malignancy-related gastroparesis, in particular paraneosplastic gastroparesis. • Paraneoplastic syndromes such as gastroparesis are common in patients with neuroendocrine tumours, especially small cell lung carcinoma and pancreatic neuroendocrine carcinoma. • Nasogastric tube (NGT) insertion has not been studied in the management of gastroparesis in palliative care settings. What this paper adds? • Palliative care units can successfully provide invasive management, such as NGT insertion, for symptom control. • NGT insertion combined with erythromycin can have a positive impact on symptoms relating to paraneoplastic gastroparesis. • Oral erythromycin following initial intravenous (IV) erythromycin can continue to be effective in paraneoplastic gastroparesis.
1Palliative
and Supportive Care Unit, Monash Medical Centre Clayton, Monash Health, Clayton, VIC, Australia 2Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, VIC, Australia 3Monash Health, Clayton, VIC, Australia
Corresponding author: Michael Franco, Palliative and Supportive Care Unit, McCulloch House, Monash Medical Centre Clayton, Monash Health, 246 Clayton Rd, Clayton, VIC 3168, Australia. Email: [email protected]
987
Franco and Koulaeva Implications for practice, theory or policy
• T here is need for research in the use of erythromycin and NGT insertion in gastroparesis, especially in the palliative patient population. • The use of erythromycin may be effective in malignancy-associated gastroparesis. • This article also further supports the use of novel management strategies in palliative care units to alleviate symptoms, potentially allowing patients to be discharged home.
Background Nausea and vomiting are two of the most common symptoms that require management in a typical palliative care patient population. While the aetiology of nausea and vomiting is often easy to discern, there is a subset of this patient population in which the causes are less clear and thus management becomes a significant challenge. One of the less common but still under-recognised causes of nausea and vomiting is gastroparesis.1 In palliative medicine, the majority of cases of gastroparesis seen will be in patients with metastatic malignancy. However, with its ever-increasing prevalence, greater numbers of patients with gastroparesis secondary to the autonomic neuropathy of type II diabetes mellitus are likely to be incidentally encountered. There are numerous aetiologies of gastroparesis relevant to patients with metastatic malignancy, including paraneoplastic syndromes, as a side effect from chemo- or radiotherapy and infiltration of the coeliac plexus. Particular primary malignancies are most associated with paraneoplastic gastroparesis. The most common are tumours of neuroendocrine origin, for example, pancreatic cancer, small cell lung cancer and carcinoid tumours.2 The pathogenesis in these cancers appears to be related to the prevalence of anti-Hu antibodies, which mediate autonomic dysfunction that leads to gastroparesis in these patients. Their prevalence is highest in small cell lung cancer, where one case series of 196 patients found 16% to be anti-Hu antibody positive.3 The treatment of gastroparesis of all causes is often challenging, and current literature is limited to studies of prokinetic agents, botulinum toxin injection and, in severe refractory cases, surgery and gastro-electrical stimulation. While there are several small trials and case studies regarding erythromycin in diabetic and idiopathic gastroparesis,4,5 there has only been a single case study published in palliative medicine literature.6 The literature on treatment of paraneoplastic gastroparesis is even more limited, and currently, only a single review article detailing general recommendations drawn from non-malignant literature has been published.7 At present, there are no published literature on the use of erythromycin in malignancy-induced gastroparesis or the combination of nasogastric tube (NGT) and erythromycin in gastroparesis of any cause.
We report a case of a patient with a pancreatic neuroendocrine cancer who was successfully treated with NGT insertion, followed by intravenous (IV) and then oral erythromycin.
Case presentation A 72 year-old man with a neuroendocrine pancreatic tumour requiring multiple biliary and duodenal stents was referred to our palliative care unit (PCU) by an acute gastroenterology unit for symptom management. On admission to gastroenterology, the patient presented with a month-long history of progressive nausea and vomiting, weight loss and lethargy. Prior to this, the patient had recently moved to a residential care facility and was ambulating independently. Initial endoscopy revealed malignant infiltration of the duodenal stent, which was successfully replaced; however, the severe nausea and vomiting continued. An ensuing barium swallow revealed minimal contrast in the first part of duodenum, retrograde flow into the biliary tree and no contrast into third part of the duodenum. Repeat endoscopy a day later showed a dilated stomach, no appreciable biliary obstruction and completely patent duodenal and biliary stents with contrast freely flowing into the distal duodenum. Thus, the final diagnosis from the gastroenterology unit was of paraneoplastic gastroparesis for which metoclopramide 60 mg, haloperidol 1.5 mg via continuous subcutaneous infusion (CSCI) and domperidone 20 mg TDS orally was commenced in an attempt to improve gastric emptying and relieve symptoms. On admission to PCU, the patient was still intolerant of any oral intake, had abdominal pain and reduced bowel motions and persistent vomiting, each of large volume. On examination, there was epigastric tenderness and hyperactive bowel sounds.
Case management After admission to the PCU, the patient was very reluctant to ambulate as he felt the nausea and vomiting were directly related to mobility. At this point, a NGT was offered. Following NGT insertion, there was initial improvement with cessation of vomiting, and the patient was subsequently able to ambulate around the ward. However, symptoms recurred 2 days later.
988
Palliative Medicine 28(7)
Given that the patient’s primary goal was to return back to his residential facility, he was tolerating oral intake, other symptoms had resolved and he was ambulant, the patient was discharged after a 21-day stay in the PCU. The patient’s symptoms remained well controlled with no change in medication until his death later that month.
given intravenously. While it was previously thought that this action directly stimulates peristalsis, more recently, it has been suggested that the major action of motilin and motilin agonists at therapeutic doses is to facilitate cholinergic mediation of gastrointestinal smooth muscle.11 To date, studies of erythromycin have been limited by small patient numbers, not using validated symptom assessment scores or having symptom control as a primary endpoint.12 Additionally, there have been no specific studies of its use in palliative patients or in gastroparesis of a paraneoplastic or direct malignant cause. Multiple pharmacokinetic studies have shown erythromycin to be more effective than metoclopramide in stimulation of gastric emptying as measured by residual gastric volume and intestinal drug absorption after administration.4 Additionally, other studies of gastroparetic patients show correlation between these objective measures and patient symptoms; thus, it is reasonable to postulate that erythromycin may be the more effective treatment.1 There is little evidence regarding the use of NGT drainage and decompression in patients with gastroparesis or regarding the use of NGTs in PCUs. Current literature is limited to the exploratory use of venting enterostomy in pseudo-obstruction in two retrospective case series (which included paediatric patients) and concluded that enterostomy can improve symptoms and reduce hospitalisation in selected patients.13
Discussion
Conclusion
The patient discussed in this case is typical of patients with gastroparesis of paraneoplastic aetiology. Neuroendocrine tumours have higher rates of paraneoplastic syndromes than other malignancies and make this an important differential diagnosis for the patient’s refractory nausea and vomiting.2 The data for treatment of these syndromes are limited. As with other paraneoplastic syndromes, improvement of symptoms may be seen if the underlying cancer is able to be treated.8 Clearly, this may not be a viable option once a patient has been referred for palliative care input, and thus, other symptomatic treatments are required. The best data exist for pharmacotherapy with the prokinetic medications metoclopramide or erythromycin.1 Metoclopramide’s facilitation of gastric emptying is via agonism of 5-HT4 receptors on enteric neurones that promote gastric emptying by enhancing antral contractions.9 The role of metoclopramide’s D2 receptor activity appears to relate more to its antiemetic function rather than directly promote prokinesis.10 Current literature in malignancyassociated gastroparesis is limited to one prospective case series of 10 patients which showed subjective and objective clinical benefit with administration of metoclopramide.4 Erythromycin is a motilin agonist that acts indirectly on gastric smooth muscle and is particularly potent when
Paraneoplastic gastroparesis is relatively common, underrecognised and can cause significant morbidity and negative impact on quality of life in patients with small cell and other neuroendocrine carcinomas. In many palliative patients, treatment of the underlying malignancy is no longer possible, and hence, a symptom-based approach is required. In the case described, an approach of NGT decompression and drainage of stomach contents followed by IV and oral erythromycin was effective in improving symptoms. Further studies into the prevalence and best management of paraneoplastic gastroparesis – in particular the use of NGT insertion and erythromycin – are warranted.
Given the symptom recurrence, the motilin agonist erythromycin was commenced. Initially, erythromycin was administered intravenously at 180 mg TDS (3 mg/kg, patient weight ~60 kg). The NGT became dislodged the next day, and it was decided to trial continuing the erythromycin without NGT reinsertion. Two days following commencement of erythromycin, the patient had significant symptom resolution. He was painfree, had moved his bowels, was tolerating a soft diet with no associated nausea or vomiting and was ambulating independently. IV erythromycin was continued for a total of 5 days. At this point, the erythromycin was changed to an oral maintenance dose of 125 mg oral TDS, and metoclopramide was also changed to oral administration the same day. Following the change to the oral route of administration, the patient had several episodes of nausea and vomiting; however, these settled with an increase in dose of metoclopramide to 20 mg orally QID.
Case outcome
Acknowledgements The patient gave written informed consent. We would like to acknowledge his contribution and are indebted to him for allowing this report to be written.
Declaration of conflicting interests The authors declare that there is no conflict of interest.
Funding This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.
Franco and Koulaeva References 1. Horowitz M, Su YC, Rayner CK, et al. Gastroparesis: prevalence, clinical significance and treatment. Can J Gastroenterol 2001; 15: 805–813. 2. Nguyen-tat M, Pohl J, Gunter E, et al. Severe paraneoplastic gastroparesis associated with anti-Hu antibodies preceding the manifestation of small-cell lung cancer. Z Gastroenterol 2008; 46: 274–278. 3. Graus F, Dalmou J, Rene R, et al. Anti-Hu antibodies in patients with small-cell lung cancer: association with complete response to therapy and improved survival. J Clin Oncol 1997; 15: 2866–2872. 4. Janssens J, Peeters TL, Vantrappen G, et al. Improvement of gastric emptying in diabetic gastroparesis by erythromycin. Preliminary studies. N Engl J Med 1990; 322: 1028–1031. 5. Janssen P, Harris MS, Jones M, et al. The relation between symptom improvement and gastric emptying in the treatment of diabetic and idiopathic gastroparesis. Am J Gastroenterol 2013; 108: 1382–1391. 6. Hunter A, Regnard C and Armstrong C. The use of longterm, low-dose erythromycin in treating persistent gastric stasis. J Pain Symptom Manage 2005; 29: 430–433.
989 7. Donthireddy KR, Ailawadhi S, Nasser E, et al. Malignant gastroparesis: pathogenesis and management of an underrecognized disorder. J Support Oncol 2007; 5: 355–363. 8. Caras S, Laurie S, Cronk W, et al. Case report: pancreatic cancer presenting with paraneoplastic gastroparesis. Am J Med Sci 1996; 312: 34–36. 9. Sanger GJ. Translating 5-HT4 receptor pharmacology. Neurogastroenterol Motil 2009; 21: 1235–1238. 10. Sanger GJ, Broad J and Andrews PL. The relationship between gastric motility and nausea: gastric prokinetic agents as treatments. Eur J Pharmacol 2013; 715: 10–14. 11. Broad J, Mukherjee S, Samadi M, et al. Regional- and agonist-dependent facilitation of human neurogastrointestinal functions by motilin receptor agonists. Br J Pharmacol 2012; 167: 763–774. 12. Maganti K, Onyemere K and Jones MP. Oral erythromycin and symptomatic relief of gastroparesis: a systematic review. Am J Gastroenterol 2003; 98: 259–263. 13. Murr MM, Sarr MG and Camilleri M. The surgeon’s role in the treatment of chronic intestinal pseudoobstruction. Am J Gastroenterol 1995; 90: 2147–2151.
