Optimizing Peri-operative Care in Bariatric Surgery Patients
Coblijn, U.K.
2018
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Coblijn, U. K. (2018). Optimizing Peri-operative Care in Bariatric Surgery Patients.
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CHAPTER 4
The influence of prophylactic proton pump inhibitor
treatment on the development of symptomatic
marginal ulceration in Roux-en-Y gastric bypass
patients: a historic cohort study
Usha K. Coblijn, Sjoerd M. Lagarde, Steve M.M. de Castro, Sjoerd D. Kuiken, Willem F. van Tets, Bart A. van Wagensveld
Published in: Surg Obes Relat Dis, 2016 Feb;12(2):246-52
CHAPTER 4
The influence of prophylactic proton pump inhibitor
treatment on the development of symptomatic
marginal ulceration in Roux-en-Y gastric bypass
patients: a historic cohort study
Usha K. Coblijn, Sjoerd M. Lagarde, Steve M.M. de Castro, Sjoerd D. Kuiken, Willem F. van Tets, Bart A. van Wagensveld
Published in: Surg Obes Relat Dis, 2016 Feb;12(2):246-52
68
Abstract:
Background and study aim: Marginal ulceration (MU) at the gastrojejunostomy (GJS) is a
serious complication after laparoscopic Roux-en- Y gastric bypass surgery (LRYGB) and occurs in 1 to 16% of the patients. Proton pump inhibitors (PPI) might lower the occurrence of these ulcers. The aim of the present study is to evaluate the effect of six months prophylactic usage of PPI’s on the development of marginal ulceration and compare this to a historic patient control group.
Methods: A consecutive database of patients who underwent LRYGB from November 2007
till September 2012 in a single institution was retrospectively reviewed. From august 2011 patients received a standard dose of Pantozol 40 mg® once daily directly postoperative
for 6 months. No standard PPI prophylaxis was administered prior to august 2011 and the patients not using PPI’s in this historic cohort served as control group.
Results: A total of 610 patients underwent LRYGB of which 128 patients (21.0%) underwent
revisional surgery. Postoperative PPI’s were administered in the intervention group of 337 patients compared to the historic control group existing of 273 patients. Six patients (1.2%) who received postoperative PPI’s versus 20 patients (7.3%) in the historic control group developed MU (p = 0.001). Patients using proton pump inhibitors developed less gastroin-testinal complaints postoperatively (p = < 0.001)
Conclusion: Routine usage of PPI’s reduced the occurrence of marginal ulceration after
LRYGB.
68
Abstract:
Background and study aim: Marginal ulceration (MU) at the gastrojejunostomy (GJS) is a
serious complication after laparoscopic Roux-en- Y gastric bypass surgery (LRYGB) and occurs in 1 to 16% of the patients. Proton pump inhibitors (PPI) might lower the occurrence of these ulcers. The aim of the present study is to evaluate the effect of six months prophylactic usage of PPI’s on the development of marginal ulceration and compare this to a historic patient control group.
Methods: A consecutive database of patients who underwent LRYGB from November 2007
till September 2012 in a single institution was retrospectively reviewed. From august 2011 patients received a standard dose of Pantozol 40 mg® once daily directly postoperative
for 6 months. No standard PPI prophylaxis was administered prior to august 2011 and the patients not using PPI’s in this historic cohort served as control group.
Results: A total of 610 patients underwent LRYGB of which 128 patients (21.0%) underwent
revisional surgery. Postoperative PPI’s were administered in the intervention group of 337 patients compared to the historic control group existing of 273 patients. Six patients (1.2%) who received postoperative PPI’s versus 20 patients (7.3%) in the historic control group developed MU (p = 0.001). Patients using proton pump inhibitors developed less gastroin-testinal complaints postoperatively (p = < 0.001)
Conclusion: Routine usage of PPI’s reduced the occurrence of marginal ulceration after
LRYGB.
69
Introduction
Obesity is a major health problem and the incidence is increasing worldwide (1). Bariatric
surgery is an effective treatment for morbid obesity with good long-term results (2). The
laparoscopic Roux-en-Y Gastric Bypass (LRYGB) is one of the procedures most frequently performed globally and will maintain a prominent role in the future of bariatric surgery. At present, approximately 47% of procedures performed is a LRYGB (3). This procedure has
become safe with acceptable short-term morbidity and mortality (2).
One of the long-term complications after LRYGB is development of an ulcer around the gastrojejunal anastomosis. In literature it is known as an anastomotic, marginal or ischemic ulcer. In the present paper it is referred to as a marginal ulcer (MU). The reported occurrence of MU varies between 0.6 and 16 percent (4-8).
Despite of research focusing on the development of MUs, no consensus has been reached. Location and size of the gastric pouch, use of foreign materials and tension at the side of the anastomosis resulting in ischemia all seem to have part in the pathogenesis (8-11). Patient
related factors such as diabetes, smoking, the use of anticoagulation and/or non-steroidal inflammatory drugs (NSAID’s) are also associated with the development of MU. The role of H. Pylori in MU is still unclear (5;12-16).
To prevent MU, proton pump inhibitors (PPI) are routinely prescribed in some centres, in order to reduce the acid production in the pouch (15;17;18). Generally, acid production in the pouch
should not be an issue since most of the parietal cell mass is left in the remnant stomach. However, research has shown that even though the pouch is created in the most proximal part of the stomach, in more than 10 percent of the time pouch pH is still below 4 (11;19).
The International Federation for Surgery for Obesity and Metabolic Diseases (IFSO) guidelines advise PPI’s in patients undergoing biliopancreatic diversion for the first postoperative year but do not advise routine usage after RYGB (20). The Society of American Gastrointestinal
and Endoscopic Surgery (SAGES) and the American Society for Metabolic and Bariatric Surgery (ASMBS) guidelines do not mention prophylactic PPI’s at all (21;22). If administered, the
recommended period of therapy is also unknown. In the present study, prophylactic use of PPI’s during six months was introduced in august 2011. The aim of this study was to evaluate the use of PPI’s for six months on the development of MU.
04
69
Introduction
Obesity is a major health problem and the incidence is increasing worldwide (1). Bariatric
surgery is an effective treatment for morbid obesity with good long-term results (2). The
laparoscopic Roux-en-Y Gastric Bypass (LRYGB) is one of the procedures most frequently performed globally and will maintain a prominent role in the future of bariatric surgery. At present, approximately 47% of procedures performed is a LRYGB (3). This procedure has
become safe with acceptable short-term morbidity and mortality (2).
One of the long-term complications after LRYGB is development of an ulcer around the gastrojejunal anastomosis. In literature it is known as an anastomotic, marginal or ischemic ulcer. In the present paper it is referred to as a marginal ulcer (MU). The reported occurrence of MU varies between 0.6 and 16 percent (4-8).
Despite of research focusing on the development of MUs, no consensus has been reached. Location and size of the gastric pouch, use of foreign materials and tension at the side of the anastomosis resulting in ischemia all seem to have part in the pathogenesis (8-11). Patient
related factors such as diabetes, smoking, the use of anticoagulation and/or non-steroidal inflammatory drugs (NSAID’s) are also associated with the development of MU. The role of H. Pylori in MU is still unclear (5;12-16).
To prevent MU, proton pump inhibitors (PPI) are routinely prescribed in some centres, in order to reduce the acid production in the pouch (15;17;18). Generally, acid production in the pouch
should not be an issue since most of the parietal cell mass is left in the remnant stomach. However, research has shown that even though the pouch is created in the most proximal part of the stomach, in more than 10 percent of the time pouch pH is still below 4 (11;19).
The International Federation for Surgery for Obesity and Metabolic Diseases (IFSO) guidelines advise PPI’s in patients undergoing biliopancreatic diversion for the first postoperative year but do not advise routine usage after RYGB (20). The Society of American Gastrointestinal
and Endoscopic Surgery (SAGES) and the American Society for Metabolic and Bariatric Surgery (ASMBS) guidelines do not mention prophylactic PPI’s at all (21;22). If administered, the
recommended period of therapy is also unknown. In the present study, prophylactic use of PPI’s during six months was introduced in august 2011. The aim of this study was to evaluate the use of PPI’s for six months on the development of MU.
04
70
Methods
All patients operated from November 2007 till September 2012 were entered into a consec-utive, prospective database. The only exclusion criterion was PPI usage in patients operated prior to August 2011.
Preoperative screening:
Prior to surgery, all patients were screened in a standardized multidisciplinary setting which consisted of physical, psychological and dietary evaluation. Patients underwent also routine polygraphy screening for obstructive sleep apnoea, and esophagogastroduodenoscopy to exclude lesions in the future remnant stomach including Helicobacter Pylori (H. Pylori) test by means of a mucosal biopsy and a CLO test (Kimberly-Clark Ballard Medical Products, Roswell, GA).
Surgical procedure:
A LRYGB was performed by one of the same three experienced bariatric surgeons or under their direct supervision.
The standardized procedure was performed as described in a previous study (23). The pouch
was created in the lesser curvature. The GJ was tension free stapled with an endoscopic linear stapler (Johnson and Johnson, Sommerville, NY, USA). The anterior aspect of the GJ was closed using uninterrupted VICRYL 2.0 (Ethicon inc. a Johnson and Johnson Company, Sommerville, NY, USA) or a V-locTM Wound Closure device (Covidien, Dublin, Ireland). In case
of a revisional operation, the procedure began with removal of the band followed by direct revision excluding the scar tissue. The operation time was recorded and pouch size was estimated based on number of staplers used to create the pouch.
Postoperative care
Patients were seen by the surgeon within three weeks after surgery. Postoperative follow up was performed in the same multidisciplinary setting that consisted of medical follow up, psychological evaluation and dietary advice.
Patients were referred to the surgeon if they experienced epigastric pain, pyrosis, reflux, abdominal pain, nausea or other symptoms needing further examination. Upper gastrointes-tinal endoscopy in order to examine the pouch and GJS was performed by an experienced gastroenterologist.
70
Methods
All patients operated from November 2007 till September 2012 were entered into a consec-utive, prospective database. The only exclusion criterion was PPI usage in patients operated prior to August 2011.
Preoperative screening:
Prior to surgery, all patients were screened in a standardized multidisciplinary setting which consisted of physical, psychological and dietary evaluation. Patients underwent also routine polygraphy screening for obstructive sleep apnoea, and esophagogastroduodenoscopy to exclude lesions in the future remnant stomach including Helicobacter Pylori (H. Pylori) test by means of a mucosal biopsy and a CLO test (Kimberly-Clark Ballard Medical Products, Roswell, GA).
Surgical procedure:
A LRYGB was performed by one of the same three experienced bariatric surgeons or under their direct supervision.
The standardized procedure was performed as described in a previous study (23). The pouch
was created in the lesser curvature. The GJ was tension free stapled with an endoscopic linear stapler (Johnson and Johnson, Sommerville, NY, USA). The anterior aspect of the GJ was closed using uninterrupted VICRYL 2.0 (Ethicon inc. a Johnson and Johnson Company, Sommerville, NY, USA) or a V-locTM Wound Closure device (Covidien, Dublin, Ireland). In case
of a revisional operation, the procedure began with removal of the band followed by direct revision excluding the scar tissue. The operation time was recorded and pouch size was estimated based on number of staplers used to create the pouch.
Postoperative care
Patients were seen by the surgeon within three weeks after surgery. Postoperative follow up was performed in the same multidisciplinary setting that consisted of medical follow up, psychological evaluation and dietary advice.
Patients were referred to the surgeon if they experienced epigastric pain, pyrosis, reflux, abdominal pain, nausea or other symptoms needing further examination. Upper gastrointes-tinal endoscopy in order to examine the pouch and GJS was performed by an experienced gastroenterologist.
71
Ulcer prophylaxis protocol
Patients were pre-operatively strongly advised to quit smoking and if necessary NSAIDs were replaced by non-ulcerogenic analgesics (e.g. Tramadol or Paracetamol). In august 2011 the postoperative protocol changed and all patients received a single dose of Pantozol® 40
mg daily for a period of six months. The patients who were operated prior to august 2011 did not receive a PPI and served as a historic control group.
Statistical analysis:
All data were analysed using SPSS 21.0 for Windows. (SPSS Inc. Chicago Illinois, USA). Age, gender, co-morbidities, medications and initial body mass index are examined for predictors of ulcer disease and to compare characteristics between the groups who received and those who did not receive PPI prophylaxis. The students t-test and Mann-Whitney U test were used to determine if any statistical significance existed between the continue variables and the Chi-square test was used for the dichotomous. A p value below 0.05 is considered statistical significant. Univariate predictors were subsequently multivariate analysed.
04
71
Ulcer prophylaxis protocol
Patients were pre-operatively strongly advised to quit smoking and if necessary NSAIDs were replaced by non-ulcerogenic analgesics (e.g. Tramadol or Paracetamol). In august 2011 the postoperative protocol changed and all patients received a single dose of Pantozol® 40
mg daily for a period of six months. The patients who were operated prior to august 2011 did not receive a PPI and served as a historic control group.
Statistical analysis:
All data were analysed using SPSS 21.0 for Windows. (SPSS Inc. Chicago Illinois, USA). Age, gender, co-morbidities, medications and initial body mass index are examined for predictors of ulcer disease and to compare characteristics between the groups who received and those who did not receive PPI prophylaxis. The students t-test and Mann-Whitney U test were used to determine if any statistical significance existed between the continue variables and the Chi-square test was used for the dichotomous. A p value below 0.05 is considered statistical significant. Univariate predictors were subsequently multivariate analysed.
04
72
Results:
A total of 610 patients, of which 129 (21.1%) underwent revisional surgery from laparoscopic adjustable gastric band into LRYGB, were operated between November 2007 and August 2012. The mean follow-up was 36.3 months in the intervention group with a standard devi-ation (SD) of 3.9 compared to 38.2 months in the historic control group with a SD of 18.1, in the first cohort none of the patients were lost to follow up within one year post surgery, in the latter 16 patients (5.9%) did not complete one year of follow up.
Patient characteristics
The majority of the patients were female (488 patients, 80%). The mean age was 44 years and preoperative body mass index (BMI) was 45 kg/m², Table 1. Between both groups there were significant differences in the univariate and multivariate analysis concerning the incidence of non-insulin diabetes mellitus Table 2.
Marginal ulceration
Overall, 26 patients (4.3%) developed a MU in the whole cohort. The first group of 273 patients were operated before August 2011 and did not receive routine PPI prophylaxis, they served as a historic control group. The second group of 337 patients were operated from August 2011 onwards and routinely received PPI prophylaxis (40 mg Pantozol daily) for at least six months directly after surgery. In the historic control group 20 patients (7.3%) developed a MU compared to six patients (1.2%) in the prophylactic PPI group (p = 0.002). The mean time till presentation in the historic control group was 12.8 months with a SD of 12.8 months. In the PPI group the mean time till presentation was 1.2 months with a SD of 1.9 months. Out of the six patients who developed MU in the PPI group, two patients did not take the PPI and one patient used NSAID’s one to three times a day against medical advice. In one patient pouch perforation occurred after revision of gastric band to LRYGB. She developed a marginal ulcer three weeks after the operation next to the nasogastric feeding tube. After a two-month admission, plans for discharge were made but the patient died unexpectedly from a large pulmonary embolism. Prophylactic use of PPI’s was an independent protective factor for the development of MU’s (p = 0.004) Table 2. Revisional surgery from laparoscopic adjustable gastric band to lap-aroscopic Roux-en-Y gastric bypass did not predispose for MU development since seven patients who underwent revisional surgery developed marginal ulcers compared to 122 who had revisional surgery and did not (p = 0.461).
72
Results:
A total of 610 patients, of which 129 (21.1%) underwent revisional surgery from laparoscopic adjustable gastric band into LRYGB, were operated between November 2007 and August 2012. The mean follow-up was 36.3 months in the intervention group with a standard devi-ation (SD) of 3.9 compared to 38.2 months in the historic control group with a SD of 18.1, in the first cohort none of the patients were lost to follow up within one year post surgery, in the latter 16 patients (5.9%) did not complete one year of follow up.
Patient characteristics
The majority of the patients were female (488 patients, 80%). The mean age was 44 years and preoperative body mass index (BMI) was 45 kg/m², Table 1. Between both groups there were significant differences in the univariate and multivariate analysis concerning the incidence of non-insulin diabetes mellitus Table 2.
Marginal ulceration
Overall, 26 patients (4.3%) developed a MU in the whole cohort. The first group of 273 patients were operated before August 2011 and did not receive routine PPI prophylaxis, they served as a historic control group. The second group of 337 patients were operated from August 2011 onwards and routinely received PPI prophylaxis (40 mg Pantozol daily) for at least six months directly after surgery. In the historic control group 20 patients (7.3%) developed a MU compared to six patients (1.2%) in the prophylactic PPI group (p = 0.002). The mean time till presentation in the historic control group was 12.8 months with a SD of 12.8 months. In the PPI group the mean time till presentation was 1.2 months with a SD of 1.9 months. Out of the six patients who developed MU in the PPI group, two patients did not take the PPI and one patient used NSAID’s one to three times a day against medical advice. In one patient pouch perforation occurred after revision of gastric band to LRYGB. She developed a marginal ulcer three weeks after the operation next to the nasogastric feeding tube. After a two-month admission, plans for discharge were made but the patient died unexpectedly from a large pulmonary embolism. Prophylactic use of PPI’s was an independent protective factor for the development of MU’s (p = 0.004) Table 2. Revisional surgery from laparoscopic adjustable gastric band to lap-aroscopic Roux-en-Y gastric bypass did not predispose for MU development since seven patients who underwent revisional surgery developed marginal ulcers compared to 122 who had revisional surgery and did not (p = 0.461).
73
There were no significant differences between the patients who developed a MU in both cohorts regarding the incidence of NSAID’s, corticosteroids and smoking, Table 3.
Out of 26 ulcers, 20 occurred in the group without prophylactic PPI’s. No significant differences could be found between characteristics of MUs in both groups. There were no differences in infection with H. Pylori (none of the ulcers tested were positive), location, presence of foreign materials or symptoms at presentation. A total of three perforations due to MU occurred in the historic control group compared to one perforation in the intervention group, (p = 1.000) Table 4.
Table 1. Baseline characteristics Baseline characteristics Total
N = 610 No PPI N = 273 Prophylactic PPI N = 337 P value P value multivariate Mean age, years ± SD 43.9 ± 10.6 43.5 ± 10.9 44.2 ± 10.3 0.339
-Female/male 488/122 211/62 277/60 0.154 -Mean BMI ± SD (kg/m2) 44.8 ± 6.4 45.4 ± 6.8 44.3 ± 6.0 0.081
-PPI: proton pump inhibitor
Table 2. Comorbidities and intoxications related to MU Comorbidities (N) Total N = 610 (%) No PPI N = 273 Prophylactic PPI N = 337
P Value Odd’s ratio P value multivariate Diabetes Mellitus 182 (29.9) 92 (33.8) 90 (26.7) 0. 062 -NIDDM 106 (17.4) 60 (22.1) 46 (13.6) 0.007 0.009 Dyslipidaemia 158 (26.0) 65 (24.0) 93 (27.6) 0. 352 -Hypertension 261 (42.8) 116 (42.5) 145 (43.0) 0. 934 -Gastritis 126 (23. 2) 61 (25.1) 65 (21.6) 0. 358 -Gastro-oesophageal reflux 187 (37.8) 81 (29.7) 106 (31.5) 0.659 HP infection (n = 384) 97 (27.2) 30 (29.7) 67 (26.3) 0. 512 -Corticosteroids 44 (7.2) 27 (9.9) 17 (5.0) 0.027 0.031 NSAID’s 25 (4.1) 15 (5.5) 10 (3.0) 0.150 -Smoking 113 (19.3) 55 (22.1) 58 (17.3) 0. 169 -MU (%) 26 (4.3) 20 (7.3) 6(1.2) 0.001 0.229 (0.091-0.579) 0.007 MU (%), excluding
patients with NSAIDS (n = 585)
21 (3.6) 16 (6.2) 5 (1.5) 0.003 0. 235 (0.085-0.650)
-PPI: proton pump inhibitor; NIDDM: non-insulin depended diabetes mellitus, HP: Helicobacter Pylori infection; NSAID’s: non-steroidal anti-inflammatory drugs; MU: Marginal ulcer
04
73
There were no significant differences between the patients who developed a MU in both cohorts regarding the incidence of NSAID’s, corticosteroids and smoking, Table 3.
Out of 26 ulcers, 20 occurred in the group without prophylactic PPI’s. No significant differences could be found between characteristics of MUs in both groups. There were no differences in infection with H. Pylori (none of the ulcers tested were positive), location, presence of foreign materials or symptoms at presentation. A total of three perforations due to MU occurred in the historic control group compared to one perforation in the intervention group, (p = 1.000) Table 4.
Table 1. Baseline characteristics Baseline characteristics Total
N = 610 No PPI N = 273 Prophylactic PPI N = 337 P value P value multivariate Mean age, years ± SD 43.9 ± 10.6 43.5 ± 10.9 44.2 ± 10.3 0.339
-Female/male 488/122 211/62 277/60 0.154 -Mean BMI ± SD (kg/m2) 44.8 ± 6.4 45.4 ± 6.8 44.3 ± 6.0 0.081
-PPI: proton pump inhibitor
Table 2. Comorbidities and intoxications related to MU Comorbidities (N) Total N = 610 (%) No PPI N = 273 Prophylactic PPI N = 337
P Value Odd’s ratio P value multivariate Diabetes Mellitus 182 (29.9) 92 (33.8) 90 (26.7) 0. 062 -NIDDM 106 (17.4) 60 (22.1) 46 (13.6) 0.007 0.009 Dyslipidaemia 158 (26.0) 65 (24.0) 93 (27.6) 0. 352 -Hypertension 261 (42.8) 116 (42.5) 145 (43.0) 0. 934 -Gastritis 126 (23. 2) 61 (25.1) 65 (21.6) 0. 358 -Gastro-oesophageal reflux 187 (37.8) 81 (29.7) 106 (31.5) 0.659 HP infection (n = 384) 97 (27.2) 30 (29.7) 67 (26.3) 0. 512 -Corticosteroids 44 (7.2) 27 (9.9) 17 (5.0) 0.027 0.031 NSAID’s 25 (4.1) 15 (5.5) 10 (3.0) 0.150 -Smoking 113 (19.3) 55 (22.1) 58 (17.3) 0. 169 -MU (%) 26 (4.3) 20 (7.3) 6(1.2) 0.001 0.229 (0.091-0.579) 0.007 MU (%), excluding
patients with NSAIDS (n = 585)
21 (3.6) 16 (6.2) 5 (1.5) 0.003 0. 235 (0.085-0.650)
-PPI: proton pump inhibitor; NIDDM: non-insulin depended diabetes mellitus, HP: Helicobacter Pylori infection; NSAID’s: non-steroidal anti-inflammatory drugs; MU: Marginal ulcer
04
74
MU treatment:
In the historic control group five patients needed surgery to treat the MU. In the other patients medical treatment with PPI’s alone or combined with Sucralfate® (Ulcogant, Merck BV, The
Netherlands) was sufficient. Of the patients needing surgery, four were operated due to per-foration and one because of massive bleeding that could not be controlled endoscopically. In three patients the revision was necessary because of ulcer recurrence with symptoms who could not be treated conservatively. One patient with a pouch perforation was managed conservatively with a bridging nasogastric tube.
In the patients who received PPI prophylaxis, two patients were treated with PPI’s in higher dose, three patients also received Sucralfate®.
Table 3. Smoking, NSAID’s and Corticosteroids in patients with marginal ulcers Total group N = 26 No PPI N = 20 PPI N = 6 P-value (Fishers exact) Corticosteroids 6 (23.1) 6 (30.0) 0 (0.0) 0.280 NSAID’s 5 (19.2) 4 (20.0) 1 (16.7) 1.000 Smoking 9 (39.1) 8 (47.1) 1 (16.7) 0.340 NSAIDs: non-steroidal anti-inflammatory drugs; PPI: proton pump inhibitor
Table 4. Characteristics of MU Total (N = 26) No PPI (N= 20) Prophylactic PPI (N = 6) P Value HP infection (N = 11) 0 0 0 -Suture material 6 4 2 0.596 Bleeding 4 2 2 0.218 Epigastric Burn 18 13 5 0.628 Abdominal pain 14 12 2 0.365 Vomiting 7 5 2 1.000 Perforation 4 3 1 1.000
MU: Marginal ulcer; PPI: proton pump inhibitor; HP: Helicobacter Pylori infection
74
MU treatment:
In the historic control group five patients needed surgery to treat the MU. In the other patients medical treatment with PPI’s alone or combined with Sucralfate® (Ulcogant, Merck BV, The
Netherlands) was sufficient. Of the patients needing surgery, four were operated due to per-foration and one because of massive bleeding that could not be controlled endoscopically. In three patients the revision was necessary because of ulcer recurrence with symptoms who could not be treated conservatively. One patient with a pouch perforation was managed conservatively with a bridging nasogastric tube.
In the patients who received PPI prophylaxis, two patients were treated with PPI’s in higher dose, three patients also received Sucralfate®.
Table 3. Smoking, NSAID’s and Corticosteroids in patients with marginal ulcers Total group N = 26 No PPI N = 20 PPI N = 6 P-value (Fishers exact) Corticosteroids 6 (23.1) 6 (30.0) 0 (0.0) 0.280 NSAID’s 5 (19.2) 4 (20.0) 1 (16.7) 1.000 Smoking 9 (39.1) 8 (47.1) 1 (16.7) 0.340 NSAIDs: non-steroidal anti-inflammatory drugs; PPI: proton pump inhibitor
Table 4. Characteristics of MU Total (N = 26) No PPI (N= 20) Prophylactic PPI (N = 6) P Value HP infection (N = 11) 0 0 0 -Suture material 6 4 2 0.596 Bleeding 4 2 2 0.218 Epigastric Burn 18 13 5 0.628 Abdominal pain 14 12 2 0.365 Vomiting 7 5 2 1.000 Perforation 4 3 1 1.000
MU: Marginal ulcer; PPI: proton pump inhibitor; HP: Helicobacter Pylori infection
75
Other gastro-intestinal complaints
Patients in the intervention group had less other gastro-intestinal complaints requiring gastroscopy Table 5.
Twenty (7.9%) patients complained of epigastric burn in the historic cohort group compared to 11 (3.3%) in the PPI group. Upper abdominal complaints were present in 29 (5.0%) patients of which 20 (7.9%) belonged to the historic control group while nine (2.7%) belonged to the PPI group. Furthermore, ten (1.7%) patients suffered from late postoperative vomiting, the majority (nine patients, 3.6%) belonging to the historic control group.
None of these patients had a pathologic finding at the diagnostic gastroscopy. The difference in the occurrence of symptoms between the intervention and historic control group was statistical significant for all variables.
Table 5. Gastro-intestinal complaints in patients without MU Gastro-intestinal symptoms Total (N = 584) No PPI (N= 253) Prophylactic PPI (N = 331)
P-Value Odd’s ratio (95% CI)
Epigastric Burn 31 (5.3) 20 (7.9) 11 (3.3) 0.016 0.400 (0.188-0.852) Abdominal pain 29 (5.0) 20 (7.9) 9 (2.7) 0.006 0.326 (0.146-0.728) Vomiting 10 (1.7) 9 (3.6) 1 (0.3) 0.003 0.082 (0.010-0.653) PPI: proton pump inhibitor
Ulcer recurrence
Six of the 26 patients with MU suffered from ulcer recurrence. Two of these patients needed revision of the anastomosis, one because of ulcer perforation and one because of uncon-trollable bleeding as previous described. The other four ulcers were treated conservatively, one with the adding of Sucralfate® to the PPI. Of the patients with an ulcer recurrence
five belonged to the historic control group compared to one in the intervention group, this difference was not statistical significant p = 0.094.
04
75
Other gastro-intestinal complaints
Patients in the intervention group had less other gastro-intestinal complaints requiring gastroscopy Table 5.
Twenty (7.9%) patients complained of epigastric burn in the historic cohort group compared to 11 (3.3%) in the PPI group. Upper abdominal complaints were present in 29 (5.0%) patients of which 20 (7.9%) belonged to the historic control group while nine (2.7%) belonged to the PPI group. Furthermore, ten (1.7%) patients suffered from late postoperative vomiting, the majority (nine patients, 3.6%) belonging to the historic control group.
None of these patients had a pathologic finding at the diagnostic gastroscopy. The difference in the occurrence of symptoms between the intervention and historic control group was statistical significant for all variables.
Table 5. Gastro-intestinal complaints in patients without MU Gastro-intestinal symptoms Total (N = 584) No PPI (N= 253) Prophylactic PPI (N = 331)
P-Value Odd’s ratio (95% CI)
Epigastric Burn 31 (5.3) 20 (7.9) 11 (3.3) 0.016 0.400 (0.188-0.852) Abdominal pain 29 (5.0) 20 (7.9) 9 (2.7) 0.006 0.326 (0.146-0.728) Vomiting 10 (1.7) 9 (3.6) 1 (0.3) 0.003 0.082 (0.010-0.653) PPI: proton pump inhibitor
Ulcer recurrence
Six of the 26 patients with MU suffered from ulcer recurrence. Two of these patients needed revision of the anastomosis, one because of ulcer perforation and one because of uncon-trollable bleeding as previous described. The other four ulcers were treated conservatively, one with the adding of Sucralfate® to the PPI. Of the patients with an ulcer recurrence
five belonged to the historic control group compared to one in the intervention group, this difference was not statistical significant p = 0.094.
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76
Discussion:
In the present study no prophylaxis versus PPI’s and its effect on the occurrence of MUs was analysed. The group receiving prophylactic PPI’s showed a significant decrease in the occurrence of MUs, compared to the historic control without PPI’s. Next to this decrease, PPI’s protect against other complaints as abdominal pain, vomiting and epigastric burn without the presence of a MU.
The occurrence of MU after RYGB in the literature varies between 0.6 and 16% (4-8). Although
the association between MU and acid production is not proven yet, an international survey found that most surgeons prefer to treat MU with a PPIs (24). This suggests that gastric acid
plays a role in MU formation and therefore PPI prophylaxis could prevent its development. In the same survey, 88% of the respondents prescribed prophylactic PPI’s postoperative, varying in duration form one month till lifelong (24). In this study the occurrence dropped
from 7.3 to 1.2 percent.
There are several risk factors associated with MU formation. First, the use of NSAID’s is associated with the formation of MU. Retrospective analysis only allowed to determine the preoperative use of NSAID’s, which was comparable between both groups also in the patients who developed a MU. Since both groups received the same counselling on the usage of NSAID’s, which was strongly discouraged, there is no reason to assume a difference between both groups in the postoperative use of NSAID’s. However, the use of NSAID’s is hard to quantify in a retrospective study. All patients from both cohorts were preoperatively counselled to quit smoking. Although smoking behaviour was not tested by postoperative urine sample analysis for nicotine breakdown products, there is no reason to assume a higher rate of patients who quit smoking in one of both cohorts since no preoperative difference between both cohorts was present and all patients received the same counselling, nicotine was used by nine patients who developed MU and no significance was found between the patients in the intervention or the historic control group. However, one of the limitations of this retrospective study was the impossibility of the current smoking status of the patients who did not develop an ulcer, this requires a large, prospective study. The causal role of DM in the development of MU is unclear, however some studies found that patients with DM have an increased risk on MU while others did not (5;14;15). Analysis excluding patients with
non-insulin depended diabetes mellitus showed a persistent protective effect of prophylactic PPI’s on the development of postoperative MU whereas the same accounts for patients with
76
Discussion:
In the present study no prophylaxis versus PPI’s and its effect on the occurrence of MUs was analysed. The group receiving prophylactic PPI’s showed a significant decrease in the occurrence of MUs, compared to the historic control without PPI’s. Next to this decrease, PPI’s protect against other complaints as abdominal pain, vomiting and epigastric burn without the presence of a MU.
The occurrence of MU after RYGB in the literature varies between 0.6 and 16% (4-8). Although
the association between MU and acid production is not proven yet, an international survey found that most surgeons prefer to treat MU with a PPIs (24). This suggests that gastric acid
plays a role in MU formation and therefore PPI prophylaxis could prevent its development. In the same survey, 88% of the respondents prescribed prophylactic PPI’s postoperative, varying in duration form one month till lifelong (24). In this study the occurrence dropped
from 7.3 to 1.2 percent.
There are several risk factors associated with MU formation. First, the use of NSAID’s is associated with the formation of MU. Retrospective analysis only allowed to determine the preoperative use of NSAID’s, which was comparable between both groups also in the patients who developed a MU. Since both groups received the same counselling on the usage of NSAID’s, which was strongly discouraged, there is no reason to assume a difference between both groups in the postoperative use of NSAID’s. However, the use of NSAID’s is hard to quantify in a retrospective study. All patients from both cohorts were preoperatively counselled to quit smoking. Although smoking behaviour was not tested by postoperative urine sample analysis for nicotine breakdown products, there is no reason to assume a higher rate of patients who quit smoking in one of both cohorts since no preoperative difference between both cohorts was present and all patients received the same counselling, nicotine was used by nine patients who developed MU and no significance was found between the patients in the intervention or the historic control group. However, one of the limitations of this retrospective study was the impossibility of the current smoking status of the patients who did not develop an ulcer, this requires a large, prospective study. The causal role of DM in the development of MU is unclear, however some studies found that patients with DM have an increased risk on MU while others did not (5;14;15). Analysis excluding patients with
non-insulin depended diabetes mellitus showed a persistent protective effect of prophylactic PPI’s on the development of postoperative MU whereas the same accounts for patients with
77
reflux disease Table 2. The use of corticosteroids also differed between the groups but still a protective effect of PPI’s remained. The multivariate analysis shows that although there are preoperative differences between the two groups, the usage of prophylactic PPI’s is still independently associated with a lower occurrence of MU. Most patients were screened for Helicobacter Pylori (H. Pylori) preoperatively. The presence of H. Pylori was analysed in eleven patients with MU in the present study at the time of diagnosis and all these patients tested negative. Moreover, most of the literature found no association between H. Pylori and MU formation. There is evidence that MU’s are formed by a different pathophysiology than general peptic ulcer disease (15;18; 25).
The prophylactic use of PPI’s has been debated (24;26). As previous mentioned 88% of the
surgeons turned out to be prescribing prophylactic PPI’s for three months after surgery with a range of 1 to 6 months (24). No rationale is given for the standard prophylactic use of
PPI’s nor for the duration of prophylactic usage. In this cohort, the six months course was chosen, however, no evidence for duration of prophylactic prescription exists. Two studies describe the protective effects of PPI usage against de formation of MUs (15;18). However,
due to the differences in the occurrence of MU reported in literature, it is difficult to assess the real effect of prophylaxis. Furthermore, the follow up time in the studies was short. In the study of Garrido et al. 118 subjects were analysed with a follow up of 60 days and all received PPI’s for the entire period of follow up. The occurrence of MU was 7.6% in the entire group and no higher risk for the usage of NSAID’s was found (18). d’Hondt et al compared
449 patients in which half received PPI prophylaxis for one month and the other half did not. The minimal follow up was six months and the occurrence of MU was 15.6% in the control group compared to 0% in the group with prophylactic use of PPI’s (15). In the present study,
the follow up was at least 15 months in two large groups showing a significant decrease in the occurrence of MU during follow up. Recently a meta-analysis was published by Wu et al. describing the prophylactic effect of PPI’s in reduction of MU after RYGB, both above mentioned studies were included. A total of 2114 patient were included, with a maximum of 571 patients in one study. Results of abstracts only were also included, impeding the assessment of the methods used. They found that patients on prophylactic PPI treatment experienced twice less ulceration compared to the non-PPI group (26).
The treatment of MU by proton pump inhibitors (PPI’s) is internationally accepted and advised in different guidelines (21;22). Some add Sucralfate® to their treatment, especially
when patients experience severe pain because of the ulcers. For refractory MU, more difficult
04
77
reflux disease Table 2. The use of corticosteroids also differed between the groups but still a protective effect of PPI’s remained. The multivariate analysis shows that although there are preoperative differences between the two groups, the usage of prophylactic PPI’s is still independently associated with a lower occurrence of MU. Most patients were screened for Helicobacter Pylori (H. Pylori) preoperatively. The presence of H. Pylori was analysed in eleven patients with MU in the present study at the time of diagnosis and all these patients tested negative. Moreover, most of the literature found no association between H. Pylori and MU formation. There is evidence that MU’s are formed by a different pathophysiology than general peptic ulcer disease (15;18; 25).
The prophylactic use of PPI’s has been debated (24;26). As previous mentioned 88% of the
surgeons turned out to be prescribing prophylactic PPI’s for three months after surgery with a range of 1 to 6 months (24). No rationale is given for the standard prophylactic use of
PPI’s nor for the duration of prophylactic usage. In this cohort, the six months course was chosen, however, no evidence for duration of prophylactic prescription exists. Two studies describe the protective effects of PPI usage against de formation of MUs (15;18). However,
due to the differences in the occurrence of MU reported in literature, it is difficult to assess the real effect of prophylaxis. Furthermore, the follow up time in the studies was short. In the study of Garrido et al. 118 subjects were analysed with a follow up of 60 days and all received PPI’s for the entire period of follow up. The occurrence of MU was 7.6% in the entire group and no higher risk for the usage of NSAID’s was found (18). d’Hondt et al compared
449 patients in which half received PPI prophylaxis for one month and the other half did not. The minimal follow up was six months and the occurrence of MU was 15.6% in the control group compared to 0% in the group with prophylactic use of PPI’s (15). In the present study,
the follow up was at least 15 months in two large groups showing a significant decrease in the occurrence of MU during follow up. Recently a meta-analysis was published by Wu et al. describing the prophylactic effect of PPI’s in reduction of MU after RYGB, both above mentioned studies were included. A total of 2114 patient were included, with a maximum of 571 patients in one study. Results of abstracts only were also included, impeding the assessment of the methods used. They found that patients on prophylactic PPI treatment experienced twice less ulceration compared to the non-PPI group (26).
The treatment of MU by proton pump inhibitors (PPI’s) is internationally accepted and advised in different guidelines (21;22). Some add Sucralfate® to their treatment, especially
when patients experience severe pain because of the ulcers. For refractory MU, more difficult
04
78
to treat with a PPI, reoperation is sometimes necessary (16;24). In patients with a perforation
or massive bleeding due to a MU, reoperation is required most of the time (omental patch, repair, revision) (27-29).
As a retrospective observational study of symptomatic MU development, it was not possible to identify patient compliance to the prophylaxis prescribed. The compliance in patients who did not develop postoperative complications is unknown and probably less than expected. In literature the compliance in medication among patient undergoing bariatric surgery is unknown. The general compliance to medical care after LRYGB is around 75 percent (28;30).
There is no reason to assume a higher compliance percentage in use of PPIs’.
As displayed in the results, follow up increased during the cohort. This can be explained as from halfway 2010 significant adjustments were made to increase follow up to a protocol of at least five years. Prior to treatment patients sign a contract submitting themselves to an extensive protocol existing of intensive pre and postoperative work up including a yearly medical consult.
Another limitation of this study is the performance of postoperative endoscopy only in symptomatic patients, thereby missing all asymptomatic ulcers. Literature has shown that ulcers can be present without symptoms. Twenty-eight till 100 percent of the patients do not experience the ‘typical’ ulcer symptoms as epigastric or abdominal pain, nausea and/ or vomiting and some of the patients have no symptoms at all (6;18). Although perforation
in patients with an asymptomatic MU is possible, routine performance of postoperative gastroscopy to identify asymptomatic ulcers can be discussed since the low yield and the invasive character of the diagnostic instrument.
Since there seems to be a difference in pathophysiology between late and early marginal ulcers it is not unlikely that local ischemia has a part in the development of a part of the marginal ulcers (10). However, it was not possible to investigate this relationship in the
current study. Therefore, more prospective studies are necessary to assess the difference in pathophysiology between early and late marginal ulcers subsequently to the required duration of prophylactic PPI’s.
78
to treat with a PPI, reoperation is sometimes necessary (16;24). In patients with a perforation
or massive bleeding due to a MU, reoperation is required most of the time (omental patch, repair, revision) (27-29).
As a retrospective observational study of symptomatic MU development, it was not possible to identify patient compliance to the prophylaxis prescribed. The compliance in patients who did not develop postoperative complications is unknown and probably less than expected. In literature the compliance in medication among patient undergoing bariatric surgery is unknown. The general compliance to medical care after LRYGB is around 75 percent (28;30).
There is no reason to assume a higher compliance percentage in use of PPIs’.
As displayed in the results, follow up increased during the cohort. This can be explained as from halfway 2010 significant adjustments were made to increase follow up to a protocol of at least five years. Prior to treatment patients sign a contract submitting themselves to an extensive protocol existing of intensive pre and postoperative work up including a yearly medical consult.
Another limitation of this study is the performance of postoperative endoscopy only in symptomatic patients, thereby missing all asymptomatic ulcers. Literature has shown that ulcers can be present without symptoms. Twenty-eight till 100 percent of the patients do not experience the ‘typical’ ulcer symptoms as epigastric or abdominal pain, nausea and/ or vomiting and some of the patients have no symptoms at all (6;18). Although perforation
in patients with an asymptomatic MU is possible, routine performance of postoperative gastroscopy to identify asymptomatic ulcers can be discussed since the low yield and the invasive character of the diagnostic instrument.
Since there seems to be a difference in pathophysiology between late and early marginal ulcers it is not unlikely that local ischemia has a part in the development of a part of the marginal ulcers (10). However, it was not possible to investigate this relationship in the
current study. Therefore, more prospective studies are necessary to assess the difference in pathophysiology between early and late marginal ulcers subsequently to the required duration of prophylactic PPI’s.
79
Conclusion:
The present study is the first with a relatively long term follow up comparing patients with and without PPI prophylaxis after laparoscopic Roux en Y gastric bypass. There is a protec-tive effect of PPI prophylaxis on the development of postoperaprotec-tive marginal ulceration and this study recommends routine usage of PPI’s. PPI’s also protect against other abdominal complaints as pain, epigastric burn and vomiting, decreasing the number of performed gas-troscopies without pathologic findings. More, prospective studies are required to determine the duration of prophylactic PPI administration necessary.
04
79
Conclusion:
The present study is the first with a relatively long term follow up comparing patients with and without PPI prophylaxis after laparoscopic Roux en Y gastric bypass. There is a protec-tive effect of PPI prophylaxis on the development of postoperaprotec-tive marginal ulceration and this study recommends routine usage of PPI’s. PPI’s also protect against other abdominal complaints as pain, epigastric burn and vomiting, decreasing the number of performed gas-troscopies without pathologic findings. More, prospective studies are required to determine the duration of prophylactic PPI administration necessary.
04
80
References
1. World Health Organisation. Obesity and Overweight. http://www who int/mediacentre/ factsheets/fs311/en/ 2014 August 1 [cited 2015 Jan 14];
2. Colquitt JL, Pickett K, Loveman E, Frampton GK. Surgery for weight loss in adults. Cochrane Database Syst Rev 2014;8:CD003641. 3. Buchwald H, Oien DM. Metabolic/bariatric
surgery worldwide 2011. Obes Surg 2013 Apr;23(4):427-36.
4. Capella JF, Capella RF. Staple Disruption and Marginal Ulceration in Gastric Bypass Proce-dures for Weight Reduction. Obes Surg 1996 Feb;6(1):44-9.
5. Rasmussen JJ, Fuller W, Ali MR. Marginal ulceration after laparoscopic gastric bypass: an analysis of predisposing factors in 260 patients. Surg Endosc 2007 Jul;21(7):1090-4.
6. Csendes A, Burgos AM, Altuve J, Bonacic S. Incidence of marginal ulcer 1 month and 1 to 2 years after gastric bypass: a prospective consecutive endoscopic evaluation of 442 patients with morbid obesity. Obes Surg 2009 Feb;19(2):135-8.
7. Sanyal AJ, Sugerman HJ, Kellum JM, Engle KM, Wolfe L. Stomal complications of gastric bypass: incidence and outcome of therapy. Am J Gastroenterol 1992 Sep;87(9):1165-9.
8. Sapala JA, Wood MH, Sapala MA, Flake TM, Jr. Marginal ulcer after gastric bypass: a prospective 3-year study of 173 patients. Obes Surg 1998 Oct;8(5):505-16.
9. Capella JF, Capella RF. Gastro-gastric fistulas and marginal ulcers in gastric bypass procedures for weight reduction. Obes Surg 1999 Feb;9(1):22-7.
10. Bendewald FP, Choi JN, Blythe LS, Selzer DJ, Ditslear JH, Mattar SG. Comparison of hand-sewn, linear-stapled, and circular-sta-pled gastrojejunostomy in laparoscopic Roux-en-Y gastric bypass. Obes Surg 2011 Nov;21(11):1671-5.
11. Coblijn UK, Goucham AB, Lagarde SM, Kuiken SD, van Wagensveld BA. Development of ulcer disease after Roux-en-Y gastric bypass, incidence, risk factors, and patient presen-tation: a systematic review. Obes Surg 2014 Feb;24(2):299-309.
12. Yang CS, Lee WJ, Wang HH, Huang SP, Lin JT, Wu MS. The influence of Helicobacter pylori infection on the development of gastric ulcer in symptomatic patients after bariatric surgery. Obes Surg 2006 Jun;16(6):735-9.
13. Hartin CW, Jr., ReMine DS, Lucktong TA. Preoperative bariatric screening and treatment of Helicobacter pylori. Surg Endosc 2009 Nov;23(11):2531-4.
14. Azagury DE, Abu Dayyeh BK, Greenwalt IT, Thompson CC. Marginal ulceration after Roux-en-Y gastric bypass surgery: characteristics, risk factors, treatment, and outcomes. Endoscopy 2011 Nov;43(11):950-4.
15. D’Hondt MA, Pottel H, Devriendt D, Van RF, Vansteenkiste F. Can a short course of prophy-lactic low-dose proton pump inhibitor therapy prevent stomal ulceration after laparoscopic Roux-en-Y gastric bypass? Obes Surg 2010 May;20(5):595-9.
16. Caruana JA, McCabe MN, Smith AD, Panemanglore VP, Sette CD. Risk of massive upper gastrointestinal bleeding in gastric bypass patients taking clopidogrel. Surg Obes Relat Dis 2007 Jul;3(4):443-5.
80
References
1. World Health Organisation. Obesity and Overweight. http://www who int/mediacentre/ factsheets/fs311/en/ 2014 August 1 [cited 2015 Jan 14];
2. Colquitt JL, Pickett K, Loveman E, Frampton GK. Surgery for weight loss in adults. Cochrane Database Syst Rev 2014;8:CD003641. 3. Buchwald H, Oien DM. Metabolic/bariatric
surgery worldwide 2011. Obes Surg 2013 Apr;23(4):427-36.
4. Capella JF, Capella RF. Staple Disruption and Marginal Ulceration in Gastric Bypass Proce-dures for Weight Reduction. Obes Surg 1996 Feb;6(1):44-9.
5. Rasmussen JJ, Fuller W, Ali MR. Marginal ulceration after laparoscopic gastric bypass: an analysis of predisposing factors in 260 patients. Surg Endosc 2007 Jul;21(7):1090-4.
6. Csendes A, Burgos AM, Altuve J, Bonacic S. Incidence of marginal ulcer 1 month and 1 to 2 years after gastric bypass: a prospective consecutive endoscopic evaluation of 442 patients with morbid obesity. Obes Surg 2009 Feb;19(2):135-8.
7. Sanyal AJ, Sugerman HJ, Kellum JM, Engle KM, Wolfe L. Stomal complications of gastric bypass: incidence and outcome of therapy. Am J Gastroenterol 1992 Sep;87(9):1165-9.
8. Sapala JA, Wood MH, Sapala MA, Flake TM, Jr. Marginal ulcer after gastric bypass: a prospective 3-year study of 173 patients. Obes Surg 1998 Oct;8(5):505-16.
9. Capella JF, Capella RF. Gastro-gastric fistulas and marginal ulcers in gastric bypass procedures for weight reduction. Obes Surg 1999 Feb;9(1):22-7.
10. Bendewald FP, Choi JN, Blythe LS, Selzer DJ, Ditslear JH, Mattar SG. Comparison of hand-sewn, linear-stapled, and circular-sta-pled gastrojejunostomy in laparoscopic Roux-en-Y gastric bypass. Obes Surg 2011 Nov;21(11):1671-5.
11. Coblijn UK, Goucham AB, Lagarde SM, Kuiken SD, van Wagensveld BA. Development of ulcer disease after Roux-en-Y gastric bypass, incidence, risk factors, and patient presen-tation: a systematic review. Obes Surg 2014 Feb;24(2):299-309.
12. Yang CS, Lee WJ, Wang HH, Huang SP, Lin JT, Wu MS. The influence of Helicobacter pylori infection on the development of gastric ulcer in symptomatic patients after bariatric surgery. Obes Surg 2006 Jun;16(6):735-9.
13. Hartin CW, Jr., ReMine DS, Lucktong TA. Preoperative bariatric screening and treatment of Helicobacter pylori. Surg Endosc 2009 Nov;23(11):2531-4.
14. Azagury DE, Abu Dayyeh BK, Greenwalt IT, Thompson CC. Marginal ulceration after Roux-en-Y gastric bypass surgery: characteristics, risk factors, treatment, and outcomes. Endoscopy 2011 Nov;43(11):950-4.
15. D’Hondt MA, Pottel H, Devriendt D, Van RF, Vansteenkiste F. Can a short course of prophy-lactic low-dose proton pump inhibitor therapy prevent stomal ulceration after laparoscopic Roux-en-Y gastric bypass? Obes Surg 2010 May;20(5):595-9.
16. Caruana JA, McCabe MN, Smith AD, Panemanglore VP, Sette CD. Risk of massive upper gastrointestinal bleeding in gastric bypass patients taking clopidogrel. Surg Obes Relat Dis 2007 Jul;3(4):443-5.
81
17. Kalaiselvan R, Exarchos G, Hamza N, Ammori BJ. Incidence of perforated gastro-jejunal anastomotic ulcers after laparoscopic gastric bypass for morbid obesity and role of laparos-copy in their management. Surg Obes Relat Dis 2012 Jul;8(4):423-8.
18. Garrido Jr AB, Rossi M, Lima Jr SE, Brenner AS, Gomes Jr CA. Early marginal ulcer following Roux-en-Y gastric bypass under proton pump inhibitor treatment: prospective multicentric study. Arq Gastroenterol 2010 Apr;47(2):130-4. 19. Hedberg J, Hedenstrom H, Sundbom M. Wireless
pH-metry at the gastrojejunostomy after Roux-en-Y gastric bypass: a novel use of the BRAVO system. Surg Endosc 2011 Jul;25(7):2302-7. 20. Fried M, Yumuk V, Oppert JM, Scopinaro N,
Torres A, Weiner R, et al. Interdisciplinary European guidelines on metabolic and bariatric surgery. Obes Surg 2014 Jan;24(1):42-55. 21. Jones DB, Provost DA, DeMaria EJ, Smith CD,
Morgenstern L, Schirmer B. Optimal manage-ment of the morbidly obese patient. SAGES appropriateness conference statement. Surg Endosc 2004 Jul;18(7):1029-37.
22. Mechanick JI, Youdim A, Jones DB, Timothy GW, Hurley DL, Molly MM, et al. Clinical practice guidelines for the perioperative nutritional, met-abolic, and nonsurgical support of the bariatric surgery patient--2013 update: cosponsored by American Association of Clinical Endocrinolo-gists, the Obesity Society, and American Society for Metabolic & Bariatric Surgery. Surg Obes Relat Dis 2013 Mar;9(2):159-91.
23. Coblijn UK, Lagarde SM, de Castro SM, Kuiken SD, van Wagensveld BA. Symptomatic Marginal Ulcer Disease After Roux-en-Y Gastric Bypass: Incidence, Risk Factors and Management. Obes Surg 2014 Nov 8.
24. Steinemann DC, Bueter M, Schiesser M, Amygdalos I, Clavien PA, Nocito A. Management of anastomotic ulcers after Roux-en-Y gastric bypass: results of an international survey. Obes Surg 2014 May;24(5):741-6.
25. Rawlins MP, Brown CC, Schumacher DL., Effect of Helicobacter pylori on marginal ulcer and stomal stenosis after Roux-en-Y gastric bypass. Surg Obes Relat Dis. 2013 Sep-Oct;9(5):760-4. 26. Wu CY, V, SH HK, Khan J, Farrokhyar F, D’Souza
J, Gmora S, et al. Prophylactic PPI help reduce marginal ulcers after gastric bypass surgery: a systematic review and meta-analysis of cohort studies. Surg Endosc 2014 Aug 27.
27. Wendling MR, Linn JG, Keplinger KM, Mikami DJ, Perry KA, Melvin WS, et al. Omental patch repair effectively treats perforated marginal ulcer following Roux-en-Y gastric bypass. Surg Endosc 2013 Feb;27(2):384-9.
28. Wheeler AA, de la Torre RA, Fearing NM. Laparoscopic repair of perforated marginal ulcer following Roux-en-Y gastric bypass: a case series. J Laparoendosc Adv Surg Tech A 2011 Jan;21(1):57-60.
29. Felix EL, Kettelle J, Mobley E, Swartz D. Perfo-rated marginal ulcers after laparoscopic gastric bypass. Surg Endosc 2008 Oct;22(10):2128-32. 30. McVay MA, Friedman KE, Applegate KL,
Portenier DD. Patient predictors of follow-up care attendance in Roux-en-Y gastric bypass patients. Surg Obes Relat Dis 2013 Nov;9(6):956-62.
04
81
17. Kalaiselvan R, Exarchos G, Hamza N, Ammori BJ. Incidence of perforated gastro-jejunal anastomotic ulcers after laparoscopic gastric bypass for morbid obesity and role of laparos-copy in their management. Surg Obes Relat Dis 2012 Jul;8(4):423-8.
18. Garrido Jr AB, Rossi M, Lima Jr SE, Brenner AS, Gomes Jr CA. Early marginal ulcer following Roux-en-Y gastric bypass under proton pump inhibitor treatment: prospective multicentric study. Arq Gastroenterol 2010 Apr;47(2):130-4. 19. Hedberg J, Hedenstrom H, Sundbom M. Wireless
pH-metry at the gastrojejunostomy after Roux-en-Y gastric bypass: a novel use of the BRAVO system. Surg Endosc 2011 Jul;25(7):2302-7. 20. Fried M, Yumuk V, Oppert JM, Scopinaro N,
Torres A, Weiner R, et al. Interdisciplinary European guidelines on metabolic and bariatric surgery. Obes Surg 2014 Jan;24(1):42-55. 21. Jones DB, Provost DA, DeMaria EJ, Smith CD,
Morgenstern L, Schirmer B. Optimal manage-ment of the morbidly obese patient. SAGES appropriateness conference statement. Surg Endosc 2004 Jul;18(7):1029-37.
22. Mechanick JI, Youdim A, Jones DB, Timothy GW, Hurley DL, Molly MM, et al. Clinical practice guidelines for the perioperative nutritional, met-abolic, and nonsurgical support of the bariatric surgery patient--2013 update: cosponsored by American Association of Clinical Endocrinolo-gists, the Obesity Society, and American Society for Metabolic & Bariatric Surgery. Surg Obes Relat Dis 2013 Mar;9(2):159-91.
23. Coblijn UK, Lagarde SM, de Castro SM, Kuiken SD, van Wagensveld BA. Symptomatic Marginal Ulcer Disease After Roux-en-Y Gastric Bypass: Incidence, Risk Factors and Management. Obes Surg 2014 Nov 8.
24. Steinemann DC, Bueter M, Schiesser M, Amygdalos I, Clavien PA, Nocito A. Management of anastomotic ulcers after Roux-en-Y gastric bypass: results of an international survey. Obes Surg 2014 May;24(5):741-6.
25. Rawlins MP, Brown CC, Schumacher DL., Effect of Helicobacter pylori on marginal ulcer and stomal stenosis after Roux-en-Y gastric bypass. Surg Obes Relat Dis. 2013 Sep-Oct;9(5):760-4. 26. Wu CY, V, SH HK, Khan J, Farrokhyar F, D’Souza
J, Gmora S, et al. Prophylactic PPI help reduce marginal ulcers after gastric bypass surgery: a systematic review and meta-analysis of cohort studies. Surg Endosc 2014 Aug 27.
27. Wendling MR, Linn JG, Keplinger KM, Mikami DJ, Perry KA, Melvin WS, et al. Omental patch repair effectively treats perforated marginal ulcer following Roux-en-Y gastric bypass. Surg Endosc 2013 Feb;27(2):384-9.
28. Wheeler AA, de la Torre RA, Fearing NM. Laparoscopic repair of perforated marginal ulcer following Roux-en-Y gastric bypass: a case series. J Laparoendosc Adv Surg Tech A 2011 Jan;21(1):57-60.
29. Felix EL, Kettelle J, Mobley E, Swartz D. Perfo-rated marginal ulcers after laparoscopic gastric bypass. Surg Endosc 2008 Oct;22(10):2128-32. 30. McVay MA, Friedman KE, Applegate KL,
Portenier DD. Patient predictors of follow-up care attendance in Roux-en-Y gastric bypass patients. Surg Obes Relat Dis 2013 Nov;9(6):956-62.
