The Effect of Primary Surgery in Patients with De Novo Stage IV Breast Cancer with Bone Metastasis Only (Protocol BOMET MF 14-01): A Multi-Center, Prospective Registry Study.

BACKGROUND: More evidence shows that primary surgery for de novo metastatic breast cancer (BC) prolongs overall survival (OS) in selected cases. The aim of this study was to evaluate the role of locoregional treatment (LRT) in BC patients with de novo stage IV bone only metastasis (BOM). METHODS: The prospective, multicenter registry study BOMET MF14-01 was initiated in May 2014. Patients with de novo stage IV BOM BC were divided into two groups: those receiving systemic treatment (ST group) and those receiving LRT (LRT group). Patients who received LRT were further divided into two groups: ST after LRT (LRT + ST group) and ST before LRT (ST + LRT group). RESULTS: We included 505 patients in this study; 240 (47.5%) patients in the ST group and 265 (52.5%) in the LRT group. One hundred and thirteen patients (26.3%) died in the 34-month median follow-up, 85 (35.4%) in the ST group and 28 (10.5%) in LRT group. Local progression was observed in 39 (16.2%) of the patients in the ST group and 18 (6.7%) in the LRT group (p = 0.001). Hazard of death was 60% lower in the LRT group compared with the ST group (HR 0.40, 95% CI 0.30-0.54, p < 0.0001). CONCLUSION: In this prospectively maintained registry study, we found that LRT prolonged survival and decreased locoregional recurrence in the median 3-year follow-up. Timing of primary breast surgery either at diagnosis or after ST provided a survival benefit similar to ST alone in de novo stage IV BOM BC patients.

The role of loco-regional treatment in long-term quality of life in de novo stage IV breast cancer patients: protocol MF07-01Q.

BACKGROUND/OBJECTIVE: Since more solid evidence has emerged supporting the effectiveness of loco-regional treatment (LRT), clinicians consider LRT a treatment option for selected de novo stage IV breast cancer (BC) patients. This is the first report on long-term quality of life (QoL) in a cohort of patients who were randomized to receive either LRT and then systemic treatment (ST) or ST alone in the protocol MF07-01. We aimed to evaluate QoL in patients living at least 3 years since randomization using scores from the SF-12 health survey. METHODS: SF-12 (V2) forms were completed during visits of patients who were living 36 months after the randomization. We first calculated PCS-12 (Physical Health Composite Scale) and MCS-12 (Mental Health Composite Scale) scores from de novo stage IV BC patients and compared them with the scores of patients diagnosed with stage I-III BC who lived more than 3 years. Further, PCS-12 and MCS-12 scores were compared between the LRT and ST groups with de novo stage IV BC. Additionally, general health, physical functioning, role functioning, bodily pain, vitality, mental health, and social functioning were evaluated and compared between the groups. Considering age-related changes in QoL, we also compared PCS-12 and MCS-12 scores of patients below or above 55 and 65 years of age. Responses to four additional questions (compare your physical health, mental health, daily activities, and energy currently vs. at diagnosis of BC) were recorded, considering cultural differences. RESULTS: There were 81 patients in this analysis; 68% of patients (n = 55) had LRT, and 32% (n = 26) received ST. General health was good or very good in 62% (n = 34) in the LRT group and 66% (n = 17) in the ST-only group (p = 0.63). Mean PCS-12 score was 40.8 + 1.6, and mean MCS-12 score was 43.4 + 2.0 (p = 0.34 and p = 0.54, respectively). PCS-12 and MCS-12 score difference was lower than that of the general Turkish population (PCS-12 = 49.3 + 12.8 and MCS-12 = 46.8 + 13.0) and stage I-III BC patients (PCS-12 = 51.1 ± 0.5, MCS-12 = 45.7 ± 0.6). PCS-12 and MCS-12 scores were similar between the LRT and ST-only groups in patients younger and older than 55 and 65, but QoL scores were much better in stage I-III BC patients younger than 65 when compared to the scores of those with de novo stage IV BC. Although treatment with or without LRT did not affect physical health, mental health, daily activities, and energy at 3 years vs. at diagnosis of BC in de novo stage IV BC patients (p > 0.05), these variables were significantly better in stage I-III BC patients (p < 0.001). CONCLUSION: The current MF07-01Q study demonstrates that patient who had LRT has similar physical and mental health outcomes compared to ST only in a cohort of patients who lived longer than 3 years. Trial registration This study is registered on clinicaltrials.gov with identifier number NCT00557986.

Randomized Trial Comparing Resection of Primary Tumor with No Surgery in Stage IV Breast Cancer at Presentation: Protocol MF07-01.

BACKGROUND: The MF07-01 trial is a multicenter, phase III, randomized, controlled study comparing locoregional treatment (LRT) followed by systemic therapy (ST) with ST alone for treatment-naïve stage IV breast cancer (BC) patients. METHODS: At initial diagnosis, patients were randomized 1:1 to either the LRT or ST group. All the patients were given ST either immediately after randomization or after surgical resection of the intact primary tumor. RESULTS: The trial enrolled 274 patients: 138 in the LRT group and 136 in the ST group. Hazard of death was 34% lower in the LRT group than in the ST group (hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.49-0.88; p = 0.005). Unplanned subgroup analyses showed that the risk of death was statistically lower in the LRT group than in the ST group with respect to estrogen receptor (ER)/progesterone receptor (PR)(+) (HR 0.64; 95% CI 0.46-0.91; p = 0.01), human epidermal growth factor 2 (HER2)/neu(-) (HR 0.64; 95% CI 0.45-0.91; p = 0.01), patients younger than 55 years (HR 0.57; 95% CI 0.38-0.86; p = 0.007), and patients with solitary bone-only metastases (HR 0.47; 95% CI 0.23-0.98; p = 0.04). CONCLUSION: In the current trial, improvement in 36-month survival was not observed with upfront surgery for stage IV breast cancer patients. However, a longer follow-up study (median, 40 months) showed statistically significant improvement in median survival. When locoregional treatment in de novo stage IV BC is discussed with the patient as an option, practitioners must consider age, performance status, comorbidities, tumor type, and metastatic disease burden.

Lateral intercostal artery perforator flap used in salvage of exposed tissue expander of breast: case report.

Management of an exposed tissue expander in breast reconstruction patients remains a challenging problem. For large defects that cannot be repaired primarily, local flap options are limited. In this case report, we describe the use of lateral intercostal artery perforator (LICAP) flap in salvage of an exposed tissue expander of a patient who had delayed immediate breast reconstruction after mastectomy. The postoperative recovery was uneventful and tissue expansion followed by radiotherapy was well tolerated by the flap. We believe this is the first article to describe the use of LICAP flap in salvage of an exposed tissue expander of the breast due to mastectomy flap necrosis in the early postoperative period.

Primary Surgery with Systemic Therapy in Patients with de Novo Stage IV Breast Cancer: 10-year Follow-up; Protocol MF07-01 Randomized Clinical Trial.

BACKGROUND: The aim of this randomized clinical trial was to evaluate the overall survival (OS) data of patients diagnosed with de novo stage IV breast cancer (BC) who received locoregional treatment (LRT) over a 10-year follow-up. STUDY DESIGN: The MF07-01 is a 1:1 multicenter, randomized clinical trial comparing the LRT with systemic therapy (ST), where ST was given to all patients either immediately after randomization or after surgical resection of the intact primary tumor. RESULTS: A total of 278 patients were randomized and 265 patients were in the final analysis. At 10-year follow-up, survivals were 19% (95% CI 13%-28%) and 5% (95% CI 2%-12%) in the LRT group and ST group, respectively. Median survival was 46 months for the LRT group and 35 months for the ST group, and hazard of death was 29% lower in the LRT group compared with the ST group (hazard ratio [HR] 0.71; 95% CI 0.59-0.86; p = 0.0003). CONCLUSIONS: Patients with a diagnosis of de novo stage IV BC who underwent LRT followed by ST had a 14% higher chance of OS by the end of the 10-year follow-up compared with the patients who received only ST. The longer study follow-up revealed that LRT should be presented to patients when discussing treatment options.

Relationship between functional constipation and anal-retentive behavior features.

OBJECTIVES: Constipation is the most commonly seen defecation problem related to several environmental factors. Defecation is learned in the childhood anal period in which anal characteristic features appear. Problems in the childhood anal period may affect not only characters but also defecation function. This study aimed to evaluate the relationship between constipation and anal characteristic features of participants with functional constipation. MATERIAL AND METHODS: Patients with functional constipation were included into the study according to the ROME III criteria. Patients with irritable bowel disease, slow transit constipation, outlet obstruction constipation, malignancy, and psychiatric diseases were excluded from the study. Patients filled out Personality Belief Questionnaire, Hospital Anxiety and Depression Scale, and Obsessive Belief Questionnaire. The results were compared with healthy individuals. RESULTS: A total of 47 patients with functional constipation were included in the study. Avoidant, obsessive-compulsive, antisocial, narcissistic, and paranoid personality traits were found to be higher in patients with constipation than in the control group. Perfectionism/certainty, importance and control, and hospital anxiety scores were found to be higher in patients with constipation than in the control group. CONCLUSION: Constipation may be related to several factors, such as socioeconomic environment, emotional stress, age, and diet, among others. Here, it was found that anal-retentive behavior features are prominent in functional constipation. Biofeedback, which can be regarded as psychotherapy of defecation control, can be used for treatment.

Association of Serum Paraoxonase 1 Activities, Polymorphisms and Oxidative Stress in Breast Cancer Patients with Type 2 Diabetes Mellitus.

BACKGROUND: The aim of the study was to investigate the association of paraoxonase 1 (PON1) polymorphism, PON1/arylesterase (ARE) activity and oxidative stress index (OSI) in breast cancer (BC) patients with type 2 diabetes (DM). METHODS: Our study group consisted of 30 healthy women (HV group) and 66 female BC patients. The BC patients were divided into two groups: those with (n=37) and without DM (n=29) (BDM and NBDM group). Genotyping of PON1 Q192R and L55M polymorphisms were done by polymerase chain reaction (PCR) - restriction fragment length polymorphism (RFLP) method. Serum PON1/ARE enzyme activities, total oxidant status (TOS) and total antioxidant status (TAS) were analysed by spectrophotometric method. The ratio of TOS to TAS was accepted as the oxidative stress index (OSI). RESULTS: PON1 Q192R genotype frequency distribution was significantly different in the BDM group compared to the NBDM group (p=0.021). When alleles distribution was examined, R and L alleles were significantly lower, Q and M alleles were significantly higher in the BDM group than in the NBDM group (p<0.001). TOS and OSI were statistically higher in BC patients than HV group (p<0.001). CONCLUSIONS: Our results suggest that PON1 gene Q and M alleles may be the risk factors predisposing formation of BC due to increased oxidant damage seen in DM. However, these statements require further confirmation with screening PON1 polymorphism in a greater number of patients with DM, and also wide range follow-up studies are necessary for the same purpose.

Relationship of functional constipation and anal-retentive behavior features.

OBJECTIVES: Constipation is the most commonly seen defecation problem and related with several environmental factors. Learning defecation is learned in the childhood anal period in which anal characteristic features appear. Problems in the anal period of childhood may affect not only the characters but also the defecation function. We aimed to evaluate the relationship between constipation and anal characteristic features of participants with functional constipation. MATERIAL AND METHODS: Patients with functional constipation were included in the study according to the ROME III criteria. Patients with irritable bowel disease, slow transit constipation, outlet obstruction constipation, malignancy, and psychiatric diseases were excluded from the study. Patients filled out the Personality Belief Questionnaire, Hospital Anxiety and Depression Scale, and Obsessive Belief Questionnaire. The results were compared with healthy individuals. RESULTS: A total of 47 patients with functional constipation were included in the study. The avoidant, obsessive-compulsive, antisocial, narcissistic, and paranoid personality beliefs were found to be higher in patients with constipation than in the control group. Perfectionism/certainty, importance and control, and hospital anxiety scores were found to be higher in patients with constipation than in the control group. CONCLUSION: Constipation may be related to several factors, such as socioeconomic environment, emotional stress, age, and diet, among others. Here we found that anal-retentive behavior features are prominent in functional constipation. Biofeedback, which can be regarded as psychotherapy of defecation control, can be used for treatment.

Characteristics of Special Type Breast Tumors in Our Center.

OBJECTIVE: Breast cancer is a heterogeneous disease with different histological types. Ductal breast cancer constitutes the vast majority of the breast cancers. However limited data are present in the rest of breast cancers called special or rare type breast cancers. Here in this study, we tried to describe the clinical features of special type breast cancers in our center. MATERIALS AND METHODS: Retrospective descriptive study was performed in Kocaeli University School of Medicine, Department of General Surgery between January 2000 and January 2016. Women diagnosed with primary breast cancer other than ductal carcinoma were included to the study. In total, 101 patients were evaluated according to histologic types, molecular types, Tumor Node Metastasis (TNM) stages, and grades. Survival of the patients was also evaluated. RESULTS: Medullary and metaplastic types showed basal type; tubular, mucinous, micropapillary carcinoma, cribriform, lobular and apocrine tumors showed luminal type molecular pattern. Neither the existence of ductal carcinoma nor any histologic types had any effects on survival. Apocrine tumors were presented in younger ages. CONCLUSION: Histologic types of breast cancer are closely related with the molecular types of the breast cancer. Tumor size, grade, stage of the disease can show differences among histological types which might be due to the genetic background, late onset or limited number of patients. In order to achieve more significant results, multicenter national studies are needed.

Scoring Idiopathic Granulomatous Mastitis: An Effective System for Predicting Recurrence?

OBJECTIVE: Idiopathic granulomatous mastitis is a breast disease without a definitive etiology. There are no definitive classifications, scoring systems or certitudes. The aim of this study is to define the factors related to the recurrence and design a scoring system. MATERIAL AND METHODS: Patients who were admitted to the general surgery department with symptoms of granulomatous mastitis were evaluated by ultrasonography and underwent antibiotic therapy. Granulomatous mastitis is diagnosed by core biopsy and treated with steroid therapy. Patients without improvement underwent surgery and were included in the study. In total, 53 patients were included in the study. There were 8 recurrent cases. Factors related with recurrences were defined. RESULTS: Number of births over 2, duration of lactation more than 18 months, body mass index greater than 31, having fistula in physical examination, abscess collection in ultrasonographic examination, and luminal inflammation score over 2 were scored as 1. Severity score in recurrent cases were 5.1±0.6 whereas 1.9±1.0 in nonrecurrent cases. CONCLUSION: Granulomatous mastitis score is a tool targeted at predicting the risk of recurrences. The patients with these factors are more prone for recurrences.

The Relationship between Adiponectin and Breast Cancer.

OBJECTIVE: Breast cancer is the most common type of cancer in women worldwide. It is indicated that increased body mass index elevates the risk of developing breast cancer, worsens prognosis, and decreases survival. Several polymorphisms of adiponectin have been shown to affect serum levels of adiponectin and their association with breast cancer. The aim of this study was to investigate the relationship between the adiponectin 45T/G and 276 G/T gene polymorphism and breast cancer in the East Marmara region. MATERIALS AND METHODS: A case-control study was performed in 97 patients with breast cancer and 101 controls in East Marmara in order to evaluate the prevalence of adiponectin gene polymorphism at positions 45 and 276. Patients with familial breast cancer and those who had received chemotherapy or radiotherapy were excluded from the study. Adiponectin gene polymorphisms were investigated using polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP). RESULTS: Adiponectin 45T/G gene genotype frequencies of TT, TG, and GG were 61.9%, 37.1%, and 1% in patients with breast cancer, and 67.3%, 30.7%, and 2% in the control group, respectively. Adiponectin 276G/T gene genotype frequencies of GG, GT, and TT were 45.4%, 45.4%, and 9.3% in patients with breast cancer and 55.4%, 39.6%, and 5.0% in the control group, respectively. CONCLUSION: Our study showed that adiponectin 45T/G and 276 G/T gene polymorphism is not associated with breast cancer risk in patients from the East Marmara region.

Effects of chronic ethanol consumption on rat upper gastrointestinal system: functional and histologic findings.

The purpose of the present study was to determine the effect of chronic alcohol consumption on reactivity of esophageal tunica muscularis mucosae (TMM) and lower esophageal sphincter (LES) smooth muscle. Six male rats in alcohol-fed group received ethanol (7.2% v/v) in a modified liquid diet for 4 weeks. Two control groups were used; six rats in the standard diet-fed group received rat chow and water for 4 weeks. Six rats in sucrose-fed group were given sucrose and received a liquid diet. The smooth muscle reactivity of TMM and LES strips from ethanol-fed and control animals was evaluated in organ chambers. Also histologic study was undertaken to show effects of chronic alcohol consumption. Maximum contractile responses of TMM to KCl and carbachol were decreased in the ethanol-fed group compared to the control groups. Relaxant responses to serotonin were decreased in the ethanol-fed group compared to the control groups. In TMM, isoproterenol- and papaverine-induced relaxant responses were similar in the ethanol-fed and control groups. In LES smooth muscle, relaxant responses to papaverine or isoproterenol were similar in the control groups and the ethanol-fed group. There was no change in agonist potency among the groups. The relaxation response elicited by nicotine and sodium nitroprusside (SNP) or contractile response elicited by carbachol and 80 mM KCl was decreased with maximum responses and pD(2) values, in the ethanol-fed group compared to that of the control groups in LES. Decreased nNOS immunoreactivity in myenteric plexus was found in alcohol-exposed group compared to control groups. Our findings suggest that chronic alcohol consumption impairs relaxant and contractile responses of both TMM and LES smooth muscle and it may contribute to gastroesophageal reflux commonly seen after alcohol binges.

Predicting the likelihood of nonsentinel lymph node metastases in triple negative breast cancer patients with a positive sentinel lymph node: Turkish Federation of Breast Disease Associations protocol MF09-01.

BACKGROUND: Triple negative (TN) tumor has a relatively high rate of recurrence and distant metastasis, but results of studies revealed that triple positive tumor is an independent predictor of axillary lymph node involvement. Our aim was to evaluate the frequency of nonsentinel lymph node metastasis (NSLNM) involvement in operable TN breast cancer with positive sentinel lymph node (SLN) and predicting the likelihood of NSLNM in this cohort of patients by using 4 different nomograms. METHODS: A total of 128 patients with TN and SLN(+) underwent complete axillary lymph node dissection in 14 different centers in Turkey. For comparison, we used our previous multicenter MF08-01 Protocol, which identified 441 patients with estrogen receptor (ER(+)) who had a positive SLN biopsy and underwent subsequent complete axillary lymph node dissection. Turkish, Cambridge, and Stanford nomograms and the Tenon Score system were used to calculate the probability of NSLNM. RESULTS: Patients with TN tumor had a larger tumor size. The actual percentage of NSLN positivity was 41% in the TN group and 47.1% in patient with ER(+). The Tenon Score was ≤3.5 in 12% of patients with TN and ER(+); the area under the curve in the receiver operating characteristics curve were 0.53 and 0.59, respectively. Based on the Turkish, Cambridge, and Stanford nomograms, areas under the curve were 0.54, 0.53, and 0.61, respectively in patients with TN, and were 0.79, 0.72, and 0.70, respectively, in patients with ER(+). CONCLUSION: Using the Tenon Score system underestimates NSLN positivity, and tested nomograms are not good discriminators of NSLNM in patients with TN and positive SLN.

Necessity for additional incisions with the cervical collar incision to remove retrosternal goiters.

PURPOSE: Retrosternal goiters (RSGs) can be removed transcervically, but additional incisions are sometimes necessary. We examined the factors determining the need for additional incisions to remove an RSG goiter, based on our experience and on an algorithm. METHODS: Among 499 patients who underwent surgery for a goiter, 52 (10.4%) had an RSG removed via a collar incision. Additional incisions were necessary in 11 patients (21% of those with an RSG and 2.2% overall): a partial sternotomy in 4, total sternotomy in 5, and right thoracotomy in 2. RESULTS: Recurrent nerve paralysis developed in two patients and one patient had a tracheal laceration. There was no mortality. A diagnosis of adenomatous goiter was confirmed in all patients. CONCLUSIONS: Additional incisions can be made if thyroidectomy cannot be done transcervically and if the goiter extends to the level of the aortic arch. If the thyroid gland extends below the aortic arch and the lateral diameter of the goiter is greater than 10 cm, a partial sternotomy may be required. Total sternotomy is needed when an RSG extends caudally to the azygos vein, if it is located in the retrotracheal or retroesophageal space, or if it is recurrent or ectopic. Coexisting lung disorders and goiters extending to the left atrium also require thoracotomy.

Effects of caustic lye injury to the esophageal smooth muscle reactivity: in vitro study.

PURPOSE: We investigated late effects of caustic lye injury on esophageal smooth muscle reactivity in the rat model. MATERIALS AND METHODS: Male Sprague-Dawley rats were divided into two groups. Through a median laparatomy incision, abdominal esophageal segment was isolated. Orogastric and gastric (via gastrotomy) catheters were placed and tied over the isolated esophageal segment. Saline (0.9%) or 50% sodium hydroxide (1 ml) solution were instilled via orogastric catheter to the isolated segment in the control and caustic esophagus (CE group) groups, respectively. Then, the esophagus was rinsed with 0.9% saline via gastric catheter. The esophagus was removed and studied in organ chambers 28 days after the operation. RESULTS: Carbachol- and KCl-induced contractile responses of esophageal smooth muscle were significantly reduced in the CE group with decreased E(max) value compared with the control group. Relaxant responses to serotonin were significantly reduced in the CE group with decreased E(max) value compared with the control group. No significant differences were found in E(max) and pD(2) values for papaverine acting on esophageal strips from the two groups. CONCLUSION: The results provide evidence that, a surgically created caustic injury causes impaired smooth muscle reactivity that may contribute to esophageal motor dysfunction.

Polymorphisms in the MTHFR gene are associated with breast cancer.

The methylenetetrahydrofolate reductase (MTHFR) gene is a polymorphic gene involved in folate metabolism, DNA biosynthesis, methylation and genomic integrity in actively dividing cells. The MTHFR C677T and A1298C polymorphisms are likely to play an important role in the susceptibility to breast cancer. In this case-control study, we examined the role of MTHFR C677T and A1298C polymorphisms in breast cancer patients. We genotyped 118 premenopausal women with sporadic breast cancer and 193 controls, using a PCR-RFLP method. The allele frequencies of the MTHFR 677T were 31.36% in the breast cancer cases and 28.76% in the controls. The allele frequencies of the MTHFR 1298C were 37.29% in the breast cancer subjects and 31.35% in the controls. Frequencies of MTHFR C677C, C677T and T677T were 50.8, 33.9 and 14.4% in the breast cancer patients and 48.7, 45.1 and 6.2% in the controls, respectively. The results of a chi(2) analysis indicated that the MTHFR 677T allele was significantly distributed (chi(2) = 7.234; p = 0.027). Likewise, the MTHFR T677T genotype showed a 2.5-fold increased risk for breast cancer and the C1298C genotype showed a 1.9-fold increased risk for breast cancer. In the compound genotypes, T677T/A1298A and C677C/C1298C showed a 4.472- and a 2.301-fold increased risk for breast cancer (OR = 4.472, p = 0.001, and OR = 2.301, p = 0.024), respectively. In conclusion, our data suggest that the MTHFR 677T, 1298C alleles, T677T, C1298C genotypes, and C677C/C1298C and T677T/A1298A compound genotypes are genetic risk factors for premenopausal women with sporadic breast cancer.

Impaired gastric motility in the gastroesophageal reflux rat model: an in vitro study.

PURPOSE: The present study investigated the effects of acid and mixed reflux on the responsiveness of gastric smooth muscle in the gastroesophageal reflux (GER) rat model. MATERIAL AND METHODS: Three groups of rat were studied encompassing acid reflux, mixed reflux and sham operation. Acid reflux was induced by pyloric ligation (AR group) and mixed reflux was induced by jejunal ligation 1 cm distal to Treitz ligament (MR group). Similar surgical manipulations were carried out in the sham operated rats (SO group). Carbachol-, serotonin-, KCl-induced contractile response and nicotine-, sodium nitroprusside-, papaverine-induced relaxant response in isolated gastric fundus smooth muscle strips were determined using in vitro muscle technique 24 h after surgery. RESULTS: Isolated gastric fundus smooth muscle contractility to serotonin, carbachol or KCl was significantly reduced in the AR and MR groups with decreased Emax and pD(2) values compared with the SO group. Relaxant responses to nicotine was significantly increased in the AR and MR groups with increased Emax and pD(2) values compared with the SO group. Sodium nitroprusside and papaverine-induced-relaxant responses were similar in all of the groups and there was no change in agonist potency. CONCLUSION: The present study indicates that decreased contractile and increased nicotine-induced relaxant response of the gastric smooth muscle in the surgically created GER model. These findings suggest that impaired gastric smooth muscle reactivity at least in part may play a role in gastric dysmotility in GER.