**3.2.** *In-vitro* **study**

It was found that if the module is inflated with the volume and pressure as described above,upon reaching the stomach it would take, via simple arithmetic mean, 49 hours to partially empty. With this partial emptying, it could pass through the pylorus and into the intestine, a situation similar to what occurred in the experiment presented in [7]. On that, note that among the restrictive techniques already in practice, endoscopic intervention is done to remove the object from the stomach before it descends into the intestine. In the case of the CFE – in the event that it becomes lodged in the stomach between one radiography and another, meaning during a 24-hour period, we would have ample time for removing it endoscopically without causing intestinal obstruction. It is worth mentioning in a detailed analysis carried out, it was noted that studies apply synthetic prosthesis in patients as temporary substitutes for the esophagus, and they are made of diverse materials such as: silicone, *Marlex*®, Teflon®, collagen, and a mixture of collagen and silicone. The amount of time the prosthesis remained inside the body was on average from four to five weeks, from its placement until its exit which corresponds to the end of this treatment, when expelled in the feces after this period without causing intestinal obstruction. In [6], which is used as a basis for this work, among the groups evaluated, cases occurred where the latex prosthesis was expelled by the animal, without causing intestinal obstruction. Thus, the scope of radiographic evaluations adopted (every 24 hours) was done to prevent the possibility of it passing from the stomach to the intestine.

#### **3.3. Weight loss analysis experiment**

This analysis sought to verify if the diet offered was bringing about weight loss in the animals. Considering this, the food provided was initiated ten days before placing the module: the animals accepted the food well given that the ingredients used were appealing. With this procedure, weight loss did not take place in any dog. On the contrary, some animals experienced weight gain.

#### *3.3.1. Volume, speed and ingestion time*

The food provided was semi-moist, made for each dog individually with measurements calculated according to the animal's weight, as indicated by the manufacturer. When preparing the food, solid dog food was used along with meat pâté for dogs and a dietary supplement called Dudog®. With the assistance of a veterinary doctor plus the manufacturer's instructions, the dietary composition was established for each dog which is presented in Table 2.


Prosthesis for Flow Control in the Esophagus as a New Technique for the Treatment of Obesity 179

Hemoglobin (g/%) Hematocrit (%) TPP\*(g/%)

Average DP() Average DP() Average DP()

The complete blood count was collected through the Vacutainer® system, taken from the arteriovenous group in a tube with four drops of anti-coagulant (10% EDTA solution), then performing the homogenization of the samples with slow and regular movements. From the samples, hemoglobin, hematocrit (the percentage occupied by red blood cells or erythrocytes in total blood volume, because a decrease in it may indicate anaemia), and total plasma protein (TPP) were evaluated. The data collected was analyzed statistically following the Tukey test (p<0,05), in the ANOVA module of STATISTICA software, with repeated measurements and a non-parametric test, for qualitative variables. The data obtained from the blood count are described in Table 3 below, thus allowing evaluation of the effects of the esophageal module, as well as evaluating how it

GCp 8,16 0,83 30,19 3,02 7,21 0,37

GT1 8,08 0,95 30,25 3,36 7,33 0,54

**Table 3.** Evaluation of the hemoglobin, hematocrit and total plasma protein. Values do not differ (p >

It was also verified that the average values obtained from the evaluation do not differ. Therefore, it may be suggested that the method does not promote alterations in the blood tissue, since when the hemoglobin concentration was evaluated, there was no difference between the groups (p > 0,05), considering that the same result was obtained in the

However, it is known that blood count evaluations may suffer variations according to the nutritional condition of the animals, climatic factors, infections and release of blood components. Nevertheless, in this study the parameters were maintained within the

Specifically in relation to weight loss, in all of the experiments conducted in this study which involved dogs, the animals' weights were monitored. Weight loss took place to a slight extent (≈1,3%), as well as to a great extent (≈6,3%), for the weight of the dogs in the analysis presented in item 7.3 of this study, which used the module. Lower indices were observed in recently arrived dogs from the Center for Zoonoses, and the higher indices were exhibited in the dogs that had already been at the Veterinary Hospital for a longer period of

*3.3.2. Nutritional, hormonal and complete blood count* 

affects the blood tissue.

0,05). \*TPP = Total plasma protein.

hematocrit and TPP evaluations.

physiological values.

*3.3.3. Weight loss* 

**Table 2.** Amount of food offered to each dog, mixed with 1 liter of water.

The containers used were identified with name of each dog, being "deducted" from their weight at each meal offered. All meals provided were weighed after having been mixed with water in a blender. During feeding, the dog was monitored. When done eating, the container was removed and weighed again, so that the exact amount of the volume ingested, per meal per dog, was obtained.

However, it was observed that the volume of food ingestion in group GT1 was less than the volume in group GCp. The accumulation of leftovers was observed in the feeding of all subjects in group GT1, having at times volumes up to 1 kg. This fact indicated that the method restricted the volume of food consumed by the dogs, but without causing apparent discomfort. Another point that should be put forth is that in the observation, there was great care taken to verify if there was evidence of satiety after eating in the dogs with the module. To this end, the container was left longer to confirm the dog's level of satiety. Faced with this situation, the animals did not go back and enjoy the rest of the contents, even when it was offered directly to them. This fact is a strong indicator that the dogs felt satiated. The speed and the time for ingesting the food were two other items observed, given that in the first two days, it was clearly noted that in group GT1, both (time and ingestion) were greater than those in group GCp.

During the eating process, the dogs in group GT1 made pauses in their food ingestion. This decreased and later it normalized over the subsequent days. It is believed that this situation occurred due to the esophagus module accommodating itself. After, it was observed that there was an inversion, since the food ingestion time of group GT1 was reduced and the amount of food consumed became gradually less. It must also be put into evidence that each dog was offered two meals a day – one at 09:00 and another at 18:00.

#### *3.3.2. Nutritional, hormonal and complete blood count*

178 Practical Applications in Biomedical Engineering

GCp

GT1

Dog weight (kg) Solid dog food (g) Meat (spoonful) Dudog® (slices)

13,100 331 2 4

13,400 339 2 4

15,780 410 3 6

9,780 247 1 2

10,120 256 1 2

18,100 470 3 6

The containers used were identified with name of each dog, being "deducted" from their weight at each meal offered. All meals provided were weighed after having been mixed with water in a blender. During feeding, the dog was monitored. When done eating, the container was removed and weighed again, so that the exact amount of the volume

However, it was observed that the volume of food ingestion in group GT1 was less than the volume in group GCp. The accumulation of leftovers was observed in the feeding of all subjects in group GT1, having at times volumes up to 1 kg. This fact indicated that the method restricted the volume of food consumed by the dogs, but without causing apparent discomfort. Another point that should be put forth is that in the observation, there was great care taken to verify if there was evidence of satiety after eating in the dogs with the module. To this end, the container was left longer to confirm the dog's level of satiety. Faced with this situation, the animals did not go back and enjoy the rest of the contents, even when it was offered directly to them. This fact is a strong indicator that the dogs felt satiated. The speed and the time for ingesting the food were two other items observed, given that in the first two days, it was clearly noted that in group GT1, both (time and ingestion) were greater

During the eating process, the dogs in group GT1 made pauses in their food ingestion. This decreased and later it normalized over the subsequent days. It is believed that this situation occurred due to the esophagus module accommodating itself. After, it was observed that there was an inversion, since the food ingestion time of group GT1 was reduced and the amount of food consumed became gradually less. It must also be put into evidence that each

dog was offered two meals a day – one at 09:00 and another at 18:00.

**Table 2.** Amount of food offered to each dog, mixed with 1 liter of water.

ingested, per meal per dog, was obtained.

than those in group GCp.

The complete blood count was collected through the Vacutainer® system, taken from the arteriovenous group in a tube with four drops of anti-coagulant (10% EDTA solution), then performing the homogenization of the samples with slow and regular movements. From the samples, hemoglobin, hematocrit (the percentage occupied by red blood cells or erythrocytes in total blood volume, because a decrease in it may indicate anaemia), and total plasma protein (TPP) were evaluated. The data collected was analyzed statistically following the Tukey test (p<0,05), in the ANOVA module of STATISTICA software, with repeated measurements and a non-parametric test, for qualitative variables. The data obtained from the blood count are described in Table 3 below, thus allowing evaluation of the effects of the esophageal module, as well as evaluating how it affects the blood tissue.


**Table 3.** Evaluation of the hemoglobin, hematocrit and total plasma protein. Values do not differ (p > 0,05). \*TPP = Total plasma protein.

It was also verified that the average values obtained from the evaluation do not differ. Therefore, it may be suggested that the method does not promote alterations in the blood tissue, since when the hemoglobin concentration was evaluated, there was no difference between the groups (p > 0,05), considering that the same result was obtained in the hematocrit and TPP evaluations.

However, it is known that blood count evaluations may suffer variations according to the nutritional condition of the animals, climatic factors, infections and release of blood components. Nevertheless, in this study the parameters were maintained within the physiological values.

#### *3.3.3. Weight loss*

Specifically in relation to weight loss, in all of the experiments conducted in this study which involved dogs, the animals' weights were monitored. Weight loss took place to a slight extent (≈1,3%), as well as to a great extent (≈6,3%), for the weight of the dogs in the analysis presented in item 7.3 of this study, which used the module. Lower indices were observed in recently arrived dogs from the Center for Zoonoses, and the higher indices were exhibited in the dogs that had already been at the Veterinary Hospital for a longer period of

time. It is believed that this occurred because the dogs that had recently arrived were under their ideal weight.

Prosthesis for Flow Control in the Esophagus as a New Technique for the Treatment of Obesity 181

After placing the module, the animals were evaluated over a period of 15 days. No dog died and there was no exclusion. At the end of the procedures associated with the experiment, the dogs received hygiene care, food and the necessary clinical-laboratorial evaluations, in order that they be donated to owners registered in the Veterinary Hospital data bank (which

No grave alteration in appetite was observed, such as anorexia. However, all of the groups ate less than what was observed before placing the module, thus characterizing a state of hyporexia. The semi-moist food provided was of the same consistency and quantity, and accepted by all of the animals, who also did not show any clinical manifestation suggesting

In all groups, voidance was normal, present and without difficulty. But defecation took

Concerning the range of pressure values, based on the results observed here and in the pilot study in dogs, a pressure range from 60 mmHg up to 120 mmHg is suggested for modules with construction characteristics similar to those applied in this experiment. As such, an exact definition of applied pressure should be made based on the diameter of the dog's esophagus, since the greater the diameter, the greater the pressure must be. This fact must be taken into consideration and evaluated prior to the endoscopy because there is a reasonable dimensional variation, given the vast number of breeds that are found in this

Clinical observation shows that the expected outcome was achieved with the placement and fixedness of the module for GC and GT1, while preserving the dog's welfare and only minimally altering its physical condition. In groups GT2 and GT3, which used greater pressure, the dogs' state remained normal after a long period of adaptation, which altered

The esophagus was analyzed in all of the animals, including the dog belonging to group GT3 that expelled the module 20 hours after placement, and one dog in group GT2 in which the module descended to the region caudal region of the stomach 9 days after placement. It must be emphasized that in all groups, there was no visible alteration to the esophageal wall. This finding was made after endoscopic macroscopic evaluation of the dogs'

dysphagia. None of them had clinical alterations during the period following.

place with less frequency, was not daily, and had a soft consistency.

**3.4. Clinical trial** 

in fact did take place).

*3.4.1. Lack of appetite* 

*3.4.2. Absence of voiding and/or defecation* 

species, each having distinct anatomical features.

the condition of the animal for a longer period.

**3.5. Damage to the esophageal wall** 

*3.4.3. Range of pressure values* 

In this analysis in which the two groups GCp (without module) and GT1 (with module) were compared, it was observed that the group in which the module was applied (for seven days), weight loss took place. This fact is attributed to a decrease in the volume of food ingested, brought about by the module placed in the esophagus. In Table 4, data related to the dogs submitted to the test are presented. For ten days, semi-moist food, before the module's placement, was provided to the two groups and after the module's placement, the dogs remained for seven more days on the same dietary routine.

The data in Table 4 are described next. In the Start column, the original weight of the dog is presented. The GCp lines correspond to the weights of the dogs in the control group that did not use the module and the GT1 lines are of the dogs in which the module was placed. The dogs were fully fed over a period of 10 days without the module. The weight of the dogs at the end of 10 days is shown in the "10 days (final)" column. Then, the modules were installed only in group GT1, and remained in the dogs for a period of 7 days, and the final weights, after 7 days, are presented in the "7 days (final)" column. The column furthest to the right indicates the weight loss percentage in relation to the weight of the dogs in both groups on the date of the module's placement.


**Table 4.** Animal weight variation2.

<sup>2</sup> The values shown in the table are an average of the weights.

### **3.4. Clinical trial**

180 Practical Applications in Biomedical Engineering

their ideal weight.

GCp

GT1

**Table 4.** Animal weight variation2.

2 The values shown in the table are an average of the weights.

time. It is believed that this occurred because the dogs that had recently arrived were under

In this analysis in which the two groups GCp (without module) and GT1 (with module) were compared, it was observed that the group in which the module was applied (for seven days), weight loss took place. This fact is attributed to a decrease in the volume of food ingested, brought about by the module placed in the esophagus. In Table 4, data related to the dogs submitted to the test are presented. For ten days, semi-moist food, before the module's placement, was provided to the two groups and after the module's placement, the

The data in Table 4 are described next. In the Start column, the original weight of the dog is presented. The GCp lines correspond to the weights of the dogs in the control group that did not use the module and the GT1 lines are of the dogs in which the module was placed. The dogs were fully fed over a period of 10 days without the module. The weight of the dogs at the end of 10 days is shown in the "10 days (final)" column. Then, the modules were installed only in group GT1, and remained in the dogs for a period of 7 days, and the final weights, after 7 days, are presented in the "7 days (final)" column. The column furthest to the right indicates the weight loss percentage in relation to the weight of the dogs in both

> Dog weight (kg) 10 days (final)

Dog weight (kg)

13,100 13,480 14,000 (+) 3,71

13,400 13,400 13,590 (+) 1,39

15,780 16,200 16,630 (+) 2,58

9,780 9,900 9,540 (-) 3,63

10,120 12,180 11,140 (-) 8,54

18,100 19,800 17,950 (-) 9,35

7 days (final) Weight change (%)

dogs remained for seven more days on the same dietary routine.

groups on the date of the module's placement.

Dog weight (kg) Start

After placing the module, the animals were evaluated over a period of 15 days. No dog died and there was no exclusion. At the end of the procedures associated with the experiment, the dogs received hygiene care, food and the necessary clinical-laboratorial evaluations, in order that they be donated to owners registered in the Veterinary Hospital data bank (which in fact did take place).

### *3.4.1. Lack of appetite*

No grave alteration in appetite was observed, such as anorexia. However, all of the groups ate less than what was observed before placing the module, thus characterizing a state of hyporexia. The semi-moist food provided was of the same consistency and quantity, and accepted by all of the animals, who also did not show any clinical manifestation suggesting dysphagia. None of them had clinical alterations during the period following.

#### *3.4.2. Absence of voiding and/or defecation*

In all groups, voidance was normal, present and without difficulty. But defecation took place with less frequency, was not daily, and had a soft consistency.

#### *3.4.3. Range of pressure values*

Concerning the range of pressure values, based on the results observed here and in the pilot study in dogs, a pressure range from 60 mmHg up to 120 mmHg is suggested for modules with construction characteristics similar to those applied in this experiment. As such, an exact definition of applied pressure should be made based on the diameter of the dog's esophagus, since the greater the diameter, the greater the pressure must be. This fact must be taken into consideration and evaluated prior to the endoscopy because there is a reasonable dimensional variation, given the vast number of breeds that are found in this species, each having distinct anatomical features.

Clinical observation shows that the expected outcome was achieved with the placement and fixedness of the module for GC and GT1, while preserving the dog's welfare and only minimally altering its physical condition. In groups GT2 and GT3, which used greater pressure, the dogs' state remained normal after a long period of adaptation, which altered the condition of the animal for a longer period.

#### **3.5. Damage to the esophageal wall**

The esophagus was analyzed in all of the animals, including the dog belonging to group GT3 that expelled the module 20 hours after placement, and one dog in group GT2 in which the module descended to the region caudal region of the stomach 9 days after placement. It must be emphasized that in all groups, there was no visible alteration to the esophageal wall. This finding was made after endoscopic macroscopic evaluation of the dogs'

esophageal wall, after removal of the module, which was compared with the endoscopy that had been previously done. Nonetheless, after the endoscopic exam, it was observed that the entire esophageal wall was intact, i.e. a normal appearance of the esophageal wall was preserved having a bright and rosy coloring, without food residuals or ulcerations. The folds were normal as was the frequency of the peristaltic waves.

Prosthesis for Flow Control in the Esophagus as a New Technique for the Treatment of Obesity 183

placement is the esophagus – in its upper third; 2) reduction of the lumen in the esophagus works mechanically, which blocks the quantity of food going from the mouth to the stomach, limiting the ingestion speed of solid foods; 3) placement takes place by means of endoscopy; 4) no alteration to the digestive tract is made, which neither brings about dysfunction nor compromises the absorption of nutrients; the procedure does not cause esophageal lesions, compared to the "gastric band" method which causes lesions in 10% of cases; 5) similar to the other methods, there is the necessity for chewing correctly, however, upon ingesting food of improper consistency, the food comes back up (before reaching the stomach), a positive point in this treatment, since in the other methods, vomiting crises triggered by incorrect mastication may develop into anorexia and bulimia; 6) similarly to the other methods, multi-professional treatment, dietary planning and exercise are also

In this study, the results show that placing a module inflated with gas in the esophagus, does not lead to behavior alterations in the animals. In humans, this feature had already been observed in studies that use esophageal balloon applications. In [21], short esophageal balloons are used (3 cm length and 1 cm in diameter) and long balloons (16 cm in length and 0,8 cm in diameter) for measuring the pressure of the esophageal wall. In [22], notations on the pressure inside the esophagus with a long balloon led to reports that the best results are reached when measurements are made at the middle third, showing that in this region the shape of the pressure *versus* volume curve is not affected by changes in body posture. Another application to be shown is aimed at tubular prostheses used to maintain patent malignant strictures of the esophagus and seal tracheo-esophageal fistulae, when they are fully expanded, reaching 18 mm to 25 mm in diameter and 8 cm to 14 cm length [23]. In the procedures that are involved in this study, no macroscopic damage was observed in the esophageal wall where the module was placed, or in the entire length of the esophagus. A great advantage of this module in relation to the other BIB® methods and the gastric band is how simple it is to manufacture, with the raw material "latex" estimated to be low-cost, easy

As for flow control in the esophagus, there are no reports in literature of studies with this objective. This may be because no one correlated a common denominator between esophageal illnesses that reduce the diameter of the esophagus and marked weight loss. To this end, the model presented in this study seeks to promote a reduction in the esophageal

So, mainly based on the results obtained and in the experiments conducted in dogs, a new procedure is revealed here for treating cases of obesity, derived from a natural source, which imbues it with a low-cost. But, it is probable that alterations and improvements will take place in the module aiming at obtaining better results for

Thus, the results reached suggest the possibility of controlling the volume of food intake by means of a mechanical system placed in the esophagus. In obtaining results associated with weight loss – without causing significant harm or nutritional changes or alterations

necessary.

to handle and highly biocompatible.

lumen to achieve weight loss.

applying it in humans.
