orthoropic ileal neobladder has been employed in the treatment of patients with end-stage urinary bladder cancers and other diseases requiring cystectomy in humans. Intramural tunnel techniques such as the W-urinary reservoir with serous-lined extramural tunnel (WUR) have been reported to be complicated, often resulting in vesicoureteral reflux.  This research was therefore designed to replicate the WUR technique in pigs, to modify it to a hanging ureterovesical anastomosis (HUVA), and to compare surgical outcomes of the two techniques. Twenty healthy Large White gilts, 6 - 7 months of age, and weighing 34.5 ± 2.04 kg were used for the research.  They were assigned to four groups (n =5), CTR, OIN, HUVA and IRA. The CTR was the negative control group.  No surgery was carried out in animals in this group.  In the OIN and HUVA groups, the urinary bladder was excised and replaced with 40 - 45 cm of detubularized ileal segment using the WUR technique.  In the OIN, the ureters were tapered in the neobladder mucosa, while in the HUVA, 1 cm of the ureter was allowed to hang in the neobladder lumen. The IRA was the positive control group and animals in this group underwent only ileal resection and anastomosis.  Ureteral stent was implanted for the collection of urine samples and replaced with urinary catheter after the 10^th postoperative day, while blood samples were collected by venipuncture of the external jugular vein. Blood and urine samples were taken pre-operatively and on postoperative days 1, 2, 3, 7, 14, 28, 56, 84 and 112. The duration of surgery was significantly higher in the OIN and HUVA groups than in other groups.   The histology of the kidneys did not show any pathologies up to the 112^th day post-surgery, while the neobladder retained the histology of the traditional ileum up to the 112^th postoperative day. Postoperatively, mean urine pH, chloride, potassium, creatinine and blood urea nitrogen were significantly higher (P ≤ 0.05) in the OIN and HUVA groups than in the CTR and IRA groups, while serum bicarbonate and sodium concentrations were significantly lower (P ≤ 0.05) in the OIN and HUVA groups.  Urine samples from animals in all the groups tested negative for ketones, nitrites, glucose, ascorbic acid, blood, urobilinogen, leucocytes, and proteins. The frequency of complications such as diarrhoea, mucoid urine, anorexia, weakness, ureteral sternosis, metabolic acidosis, urinary tract infection, and death were higher in the OIN and HUVA groups than in the CTR and IRA groups.  It was therefore concluded that urinary bladder replacement is possible in the pigs, and that the HUVA technique is as efficient as the conventional WUR as a method for urinary bladder replacement. Use of pigs as a model for transitional research therefore has great potentials.

 TABLE OF CONTENTS

Title page                                                                                                                    i

Declaration                                                                                                                  ii

Certification                                                                                                                iii

Dedication                                                                                                                  iv

Acknowledgement                                                                                                      v

Table of Contents                                                                                                       vii

List of Tables                                                                                                              xi

List of Figures                                                                                                             xii

List of Plates                                                                                                               xiii

Abstract                                                                                                                      xiv

CHAPTER 1             INTRODUCTION                                                                1

1.1                               Background of the study                                                        1

1.2                               Statement of problems                                                            9

1.3                               Objectives of the study                                                           11

1.4                               Justification                                                                             12

CHAPTER 2             LITERATURE REVIEW                                                   14

2.1                               Pigs in research                                                                       14

2.2                               Similarities between pigs and humans                                    14

2.2.1                            The heart                                                                                 14

2.2.2                            The urinary system                                                                  15

2.3                               Anatomy of the urinary system                                              17

2.3.1                            The kidneys                                                                             17

2.3.2                            The ureter                                                                                21

2.3.3                            The urinary bladder                                                                 22

2.3.4                            The urethra                                                                              23

2.4                               Catheterization of the porcine urinary bladder                       25

2.5                               Physiology of micturition                                                       27

2.6                               Micturition in neobladder patients                                          30

2.7                               Surgeries of the urinary system                                               31

2.7.1                            Renal surgeries                                                                        31

2.7.2                            Surgeries of the ureters                                                           35

2.7.3                            Urinary bladder surgeries                                                        37

2.8                               Urinary bladder reconstruction                                               42

2.8.1                            Ureterosigmoidostomy                                                           45

2.8.2                            The sigma rectum, or Mainz II pouch                                     46

2.8.3                            The Studer neobladder                                                           46

2.8.4                            The orthotopic Kock ileal reservoir                                         47

2.8.5                            The T-pouch ileal neobladder                                     47

2.8.6                            The Padua ileal neobladder (‘‘vesica ileale Padovana’’)        48

2.8.7                            Conjoined subserosal ureteral implantation in a cross-

folded ileal reservoir (‘‘I-pouch’’).                                         49

2.8.8                                Hautmann ileal neobladder                                                     49

2.8.9                                W-reservoir with serous-lined extramural tunnel                    50

2.9                                  Antireflux mechanism                                                             51

2.10                              Complications of gastrointestinal resection                            54

2.10.1                          Resection of the stomach                                                        55

2.10.2                          Resection of the jejunum                                                        55

2.10.3                          Resection of the ileum                                                            56

2.10.4                          Terminal ileal resection                                                           57

2.10.5                          Ileocaecal valve                                                                       58

2.10.6                          Caecum                                                                                   58

2.10.7                          Colon                                                                                      59

2.11                             Metabolic disturbances associated with continent

reservoirs of digestive tract origin                                          59

2.12                             Complications of ileal neobladder                                          63

2.12.1                          Wound infection and dehiscence:                                          63

2.12.2                          Anastomotic leaks:                                                                  64

2.12.3                         Bladder stones                                                                                    64

2.12.4                          Ureteroileal strictures                                                              65

2.12.5                          Spontaneous neobladder rupture                                            66

2.12.6                          Incisional hernia                                                                      67

2.12.7                          Fistula formation                                                                     67

2.12.8                          Paralytic ileus                                                                          67

2.12.8                          Urinary retention                                                                     68

2.12.10                        Urinary incontinence                                                               68

2.13                             Preparation of the ileal neobladder                                         69

2.14                             Absorptive functions of the intestines                                                72

CHAPTER 3             MATERIALS AND METHODS                                        74

3.1                               Materials                                                                                 74

3.2                               Methods                                                                                  75

3.2.1                            Ethical approval                                                                      75

3.2.2                            Experimental animals                                                              75

3.2.3                            Experimental design                                                               76

3.2.4                            Pre-surgical evaluation                                                            76

3.2.5                            Pre-surgical preparation                                                          79

3.2.6                            Anaesthetic protocol                                                               79

3.2.7                            Surgical technique                                                                   79

3.2.8                            Postoperative care and evaluation                                          95

3.2.9                            Data analysis                                                                           95

CHAPTER 4 RESULTS AND DISCUSSION                                                      96

4.1                               RESULTS                                                                               96

4.1.1                            Gross evaluation of the neobladder                                        96

4.1.2                            Histologic evaluation of the kidneys                                      98

4.1.3                            Histology of the neobladder                                                   100

4.1.4                            Duration of the surgery                                                           102

4.1.5                            Mean urine pH                                                                        103

4.1.6                            Urine specific gravity                                                              104

4.1.7                            Mean serum chloride concentration                                        105

4.1.8                            Mean serum bicarbonate concentration                                  106

4.1.9                            Serum potassium concentration                                              107

4.1.10                          Mean serum sodium concentration                                         108

4.1.11                          Mean serum creatinine concentration                                     109

4.1.12                          Mean blood urea nitrogen concentration                                110

4.1.13                          Frequency of postoperative complications                             111

4.1.14                          Urinalysis                                                                                113

4.2                               Discussion                                                                               116

CHAPTER 5 CONCLUSION AND RECOMMENDATIONS                          126

5.1                               CONCLUSION                                                                     126

5.2                               RECOMMENDATIONS                                                       127

REFERENCES                                                                                                          129

 

 

 

 

 

LIST OF TABLES

Table 4.1:        Major complications observed in the respective groups

and their frequencies of occurrence in the various groups                  112

Table 4.2         Urinalysis of pigs in the CTRO, OIN, HUVA and IRA groups        114

 

 

 

 

LIST OF FIGURES

Fig 4.1: Duration of surgery (minutes) in the CTRO, OIN, HUVA and

IRA groups                                                                                                     102

Fig 4.2  Mean urine pH in the CTRO, OIN, HUVA and IRA groups                       103

Fig 4.3  Urine specific gravity in the CTRO, OIN, HUVA and IRA groups                        104

Fig 4.4  Mean serum chloride concentration in the CTRO, OIN, HUVA and

IRA groups                                                                                                     105

Fig 4.5  Mean serum bicarbonate concentration in the CTRO, OIN,

HUVA and IRA groups                                                                                 106

Fig 4.6  Mean serum potassium concentration in the CTRO, OIN,

HUVA and IRA groups                                                                                 107

Fig 4.7  Mean serum sodium concentration in the CTRO, OIN, HUVA

and IRA groups                                                                                              108

Fig 4.8  Mean blood creatinine concentration in the CTRO, OIN,

HUVA and IRA groups                                                                                 109

Fig 4.9  Mean blood urea nitrogen concentration in the CTRO, OIN,

HUVA and IRA groups                                                                                110

 

LIST OF PLATES

Plate 3.1. Urinary catheterization for urine collection from the urinary bladder        78

Plate 3.2. A segment of the distal ileum resected showing intact mesenteric

attachment                                                                                                      82

Plate 3.3. Suturing of the medial arms of the W-shaped ileal segment.                     83

Plate 3.4. Uniting of the lateral arms of the “W” to the sutured medial wings          84

Plate 3.5. Detubularized ileal segment showing exposed ileal mucosa                      85

Plate 3.6. The distal end of the left ureter                                                                  86

Plate 3.7. Arrows show the visceral surface of the extramural tunnel of the

neobladder                                                                                                      88

Plate 3.8. Both ureters were attached such that they did not extend into

the lumen of the neobladder.                                                                                      89

Plate 3.9. Arrow shows the ureter within the extramural tunnel, and

extending intraluminally into the neobladder.                                                90

Plate 3.10. The neobladder is formed by suturing the free borders together.

Arrow shows the sutured free borders.                                                          92

Plate 3.11. The urinary bladder (A) is being removed by transecting it

at its neck, distal to the point of attachment of the ureters.                           93

Plate 3.12.  Attaching the neobladder to the urethra                                                  94

Plate 4.1.  Organ locations in situ in the OIN and HUVA groups on day 112          97

Plate 4.2  Histology of the kidney of pig in the OIN group at day112                      98

Plate 4.3  Histology of the kidney of pig in the HUVA group at day 112                99

Plate 4.4 Histology of the ileal neobladder (x 40) in the OIN group at day 112       100

Plate 4.5  Histology of the ileal neobladder (x 40) in the HUVA group at day 112  101