Generation of Leukaemia-Derived Dendritic Cells (DCleu) to Improve Anti-Leukaemic Activity in AML: Selection of the Most Efficient Response Modifier Combinations.

Dendritic cells (DC) and leukaemia derived DC (DCleu) are potent stimulators of anti-leukaemic activity in acute myeloid leukaemia (AML) and can be generated from mononuclear cells in vitro following standard DC/DCleu-generating protocols. With respect to future clinical applications though, DC/DCleu-generating protocols specifically designed for application in a whole-blood-(WB)-environment must be established. Therefore, we developed ten new DC/DCleu-generating protocols (kits; Kit-A/-C/-D/-E/-F/-G/-H/-I/-K/-M) for the generation of DC/DCleu from leukaemic WB, containing calcium-ionophore, granulocyte-macrophage-colony-stimulating-factor (GM-CSF), tumour-necrosis-factor-alpha, prostaglandin-E1 (PGE1), prostaglandin-E2 (PGE2) and/or picibanil (OK-432). All protocols were evaluated regarding their performance in generating DC/DCleu using refined classification and/or ranking systems; DC/DCleu were evaluated regarding their performance in stimulating anti-leukaemic activity using a cytotoxicity fluorolysis assay. Overall, we found the new kits capable to generate (mature) DC/DCleu from leukaemic WB. Through refined classification and ranking systems, we were able to select Kit-I (GM-CSF + OK-432), -K (GM-CSF + PGE2) and -M (GM-CSF + PGE1) as the most efficient kits in generating (mature) DC/DCleu, which are further competent to stimulate immunoreactive cells to show an improved anti-leukaemic cytotoxicity as well. This great performance of Kit-I, -K and -M in mediating DC/DCleu-based anti-leukaemic immunity in a WB-environment in vitro constitutes an important and directive step for translating DC/DCleu-based immunotherapy of AML into clinical application.

Immunomodulatory kits generating leukaemia derived dendritic cells do not induce blast proliferation ex vivo: IPO-38 as a novel marker to quantify proliferating blasts in acute myeloid leukaemia.

(Leukaemia derived) dendritic cells (DC, DCleu) are potent stimulators of anti-leukaemic activity in acute myeloid leukaemia (AML) and can be generated with immunomodulatory kits containing granulocyte-macrophage-colony-stimulating-factor (GM-CSF), prostaglandin-E1 (PGE1), prostaglandin-E2 (PGE2) and/or picibanil (OK-321). Potential adverse effects initiated through kits, especially the proliferation of blasts, must be ruled out to ensure treatment safety. We quantified proliferating blasts with the proliferation markers CD71 and Ki-67 and the novel proliferation marker IPO-38 before and after kit treatment ex vivo. IPO-38 hereby appeared to be the most sensitive marker; a combination with CD71 may add value when assessing proliferation kinetics. Kit treatment did not or only slightly (<5%) induce blast proliferation in most cases. An induction of blast proliferation was only found in single cases and could be compensated by DCleu-induced anti-leukaemic activity in most times. Overall, we appraise kit treatment to be safe in vivo.

Role of Interferon (IFN)α in "Cocktails" for the Generation of (Leukemia-derived) Dendritic Cells (DCleu) From Blasts in Blood From Patients (pts) With Acute Myeloid Leukemia (AML) and the Induction of Antileukemic Reactions.

Strategies to stabilize remissions by specific elimination of residual acute myeloid leukemia (AML) blasts are needed. Leukemia-derived dendritic cell (DCleu/DC) generated from myeloid blasts improve antileukemic T-cell reactivity and install T-cell memory. Interferon (IFN)α-DC methods produce DCleu from chronic myeloid leukemia-patients (pts') blood. Various INFα-containing versus other DC methods were studied to produce DCleu (evaluated by flowcytometry) from AML-pts' blast-containing mononuclear (MNC) or whole blood (WB). After DCleu/DC stimulation in mixed lymphocyte cultures, T cells' potential to gain antileukemic cytotoxicity was studied and correlated with different DC methods and DCleu/DC counts. (1) Generation of DCleu/DC: (a) "IFN-GIT" [containing granulocyte macrophage-colony stimulating factor (GM-CSF)+IFNα+ tumor necrosis factor (TNF)-α] produced DC successfully (≥10% DC, ≥5% DCleu/cells) from AML-MNC (WB) in 54 (56%), "MCM-Mimic" in 76 (75%), "Picibanil" in 83 (64%), and "Calcium-ionophore" in 42 (67%) of cases. Proportions of DC subtypes in MNC (WB) were comparable with all DC methods, (b) IFNα combinations containing only GM-CSF+IFNα or only IFNα showed low efficiency to produce DCleu/DC from MNC (WB) compared with "IFN-GIT." (2) Antileukemic functionality: DCleu/DC-stimulated T cells showed improved leukemia cytotoxicity compared with blast cells or unstimulated T cells. The highest blast proliferation (=insufficient T cells) was seen with "IFN-GIT" DC-stimulated T cells. Probability to respond to immunotherapy or to obtain blast lysis of DC-stimulated T cells correlated with high proportions of DCleu/DC after DC culture, independent of DC-generating methods. (3) Cytokine release profiles: levels of interleukin-6, IFN-γ, and interleukin-2 were significantly lower in DC culture supernatants (from MNC/WB) with "IFN-GIT" compared with "MCM," "Pici," and "Ca" DC supernatants. Our data show that (1) WB culture simulates AML-pts' in vivo situation, (2) DC generation is possible from AML-MNC (WB) with IFNα-containing and other DC methods, (3) successful IFNα-DC generation needs GM-CSF+IFNα+TNF-α (IFN-GIT); however, "IFN-GIT" produces less DCleu/DC compared with other (non-IFNα) DC methods, (4) T cells stimulated with "IFN-GIT"-produced DCleu/DC yielded comparable antileukemic cytotoxicity; however, in cases without achieved blast lysis, an increased blast proliferation was observed.

Paramunity-inducing Factors (PINDs) in dendritic cell (DC) cultures lead to impaired antileukemic functionality of DC-stimulated T-cells.

INTRODUCTION: Paramunity-inducing-Factors (PINDs) consist of attenuated/inactivated viruses of various poxvirus-genera, used in veterinary medicine as non-antigen-specific, non-immunising stimulators of the innate immune system against infectious and malignant diseases. Their danger-signaling-interactions were tested for their capacity to improve leukemic antigen-presentation on DC generated from AML-patients' blasts ('DCleu') and DC-stimulation/activation of antileukemic T-cells. METHODS: We analyzed, whether the addition of PINDs during DC cultures (15 healthy, 22 leukemic donors) and mixed lymphocyte culture (MLC, n = 15) with autologous (n = 6), allogeneic (n = 2) or T-cells after stem cell transplantation (SCT; n = 7) would alter the quality and quantity of DC, the composition of T-cell-subsets, and/or their antileukemic functionality (AF) as studied by FACS and functional Fluorolysis-cytotoxicity-assays. RESULTS: Effects on 1. DC-cultures: PINDs in DC-cultures lead to increased proportions of mature DC and DCleu, but reduced proportions of viable and overall, as well as TLR4- and TLR9-expressing DC. 2. MLC: PINDs increased early (CD8+) T-cell activation (CD69+), but reduced proportions of effector-T-cells after MLC 3. AF: Presence of PINDs in DC- and MLC-cultures reduced T-cells' as well as innate cells' antileukemic functionality. 4. Cytokine-release profile: Supernatants from PIND-treated DC- and MLC-cultures resembled an inhibitory microenvironment, correlating with impaired blast lysis. CONCLUSIONS: Our data shows that addition of PINDs to DC-cultures and MLC result in a "blast-protective-capacity" leading to impaired AF, likely due to changes in the composition of T-/innate effector cells and the induction of an inhibitory microenvironment. PINDs might be promising in treating infectious diseases, but cannot be recommended for the treatment of AML-patients due to their inhibitory influence on antileukemic functionality.

Anal incontinence and bowel dysfunction after sacrocolpopexy for vaginal vault prolapse.

INTRODUCTION: This study aimed to determine the prevalence of bowel dysfunction and anal incontinence in relation to vaginal vault prolapse surgery in women hysterectomized on benign indications. METHODS: This is a case-control study where women having had sacrocolpopexy (n = 78) were compared with hysterectomized women without sacrocolpopexy (n = 233) using a bowel function questionnaire and the Cleveland Clinic Incontinence Score (CCIS). RESULTS: Sacrocolpopexy was performed on average 13.7 years (+/-11.1 SD) after the hysterectomy. Sacrocolpopexy was associated with an increased prevalence of rectal emptying difficulties (p = 0.04), incomplete rectal evacuation (p < 0.001), digitally assisted rectal emptying (p < 0.001), and use of enemas (p = 0.001). There was no overall significant difference in mean CCIS when comparing women having had vaginal vault prolapse surgery (CCIS = 2.78 +/- 4.1 SD) with those without (CCIS = 2.1 +/- 3.3 SD, p = 0.1) CONCLUSIONS: Abdominal sacrocolpopexy is associated with obstructed defecation but not anal incontinence when compared to hysterectomized controls without vaginal vault prolapse surgery.

Risk factors for vaginal vault prolapse surgery in postmenopausal hysterectomized women.

OBJECTIVE: The purpose of this study was to identify risk factors for surgery of vaginal vault prolapse in hysterectomized postmenopausal women. DESIGN: We conducted a case-control study. The cases were 117 consecutive postmenopausal hysterectomized women who underwent vaginal vault prolapse surgery at Danderyd Hospital or Karolinska Hospital, Stockholm, between 1996 and 2005. Control participants were 326 age-matched, randomly selected, hysterectomized women with no vaginal vault prolapse surgery, identified from the Swedish Inpatient Register. For participants and controls alike, data on determinants were extracted from patients' records, the Swedish Inpatient Register, and self-report questionnaires. Data were analyzed using nonparametric statistics and logistic regression. RESULTS: The questionnaire was returned by 90 of 117 participants (77%) and 233 of 326 controls (71%). The mean age at response to the questionnaire was 72.8 (+/- 9.7 SD) and 71.3 (+/- 8.7 SD) years for participants and controls, respectively. In a multivariate analysis, the only predictors at a significant level were age at hysterectomy (odds ratio = 1.04, 95% CI: 1.004-1.08), prolapse or incontinence surgery before hysterectomy (OR = 2.8, 95% CI: 1.0-7.7), and prolapse or incontinence surgery before vaginal vault surgery (OR = 9.1, 95% CI: 3.6-23.4). CONCLUSIONS: Postmenopausal women with surgically managed pelvic floor disorders are at increased risk of developing vaginal vault prolapse subsequent to a hysterectomy.

Effects of hysterectomy on bowel function: a three-year, prospective cohort study.

PURPOSE: This study was a prospective evaluation of the long-term effects of hysterectomy on bowel function using self-reported outcome measures on symptoms of constipation, rectal emptying difficulties, and anal incontinence. METHODS: In this prospective cohort study, 120 consecutive patients undergoing hysterectomy for benign conditions answered a questionnaire on bowel habits and anorectal symptoms preoperatively. Forty-four patients underwent vaginal and 76 abdominal hysterectomy. Follow-up was performed one and three years postoperatively. Data were analyzed by using multivariate regression and nonparametric statistics. RESULTS: The bowel and anorectal survey was answered by 115 of 120 patients (96 percent) after one year and 107 of 120 patients (89 percent) after three years. Abdominal hysterectomy was associated with increased anal incontinence symptoms at one-year (P < 0.01) and three-year follow-up (P < 0.01). Vaginal hysterectomy was not associated with increased anal incontinence symptoms at one year follow-up, although there was a significant increase in incontinence symptoms at the three-year follow-up (P < 0.05). Risk factor analysis indicated that a reported history of obstetric sphincter injury was correlated to an increased risk of developing posthysterectomy anal incontinence (odds ratio, 2.07; 95 percent confidence interval, 1.05-2.87; P < 0.05). There was no significant rise in constipation symptoms or rectal emptying difficulties in either cohort through the follow-up. CONCLUSIONS: Neither abdominal nor vaginal hysterectomy was associated with constipation, aggravation of constipation, or rectal emptying difficulties three years after surgery. Abdominal and vaginal hysterectomy was, however, associated with an increased risk of mild anal incontinence symptoms, and patients with a reported history of obstetric sphincter injury were at particular risk for posthysterectomy fecal incontinence.

Risk of urinary incontinence after childbirth: a 10-year prospective cohort study.

OBJECTIVE: To estimate prospectively the effect of first delivery on subjective bladder function and to assess the influence of subsequent deliveries and obstetric events METHODS: We performed a prospective, observational cohort study. During a 10-week period in 1995, 304 of 309 eligible primiparous women (98%) entered the study at the postpartum maternity ward and completed a bladder function questionnaire. The 10-year observational period was completed by 246 of 304 subjects (81%). RESULTS: Prevalence of moderate-severe stress urinary incontinence increased from 5 of 304 subjects (2%) at baseline to 27 of 229 (12%) at 10 years follow-up (P < .001). Prevalence of moderate-severe urinary urgency increased from 0 subjects (0%) at baseline to 31 of 229 (13%) at the 10-year follow-up (P < .001). The relative risk (RR) (adjusted for maternal age and parity) of moderate to severe urinary incontinence increased significantly 10 years after first delivery (RR 5.8, 95% confidence interval [CI] 1.2-33.7). At multivariable analysis adjusted for age and parity, stress urinary incontinence symptoms at 9 months and 5 years follow-up were independently associated with the presence of symptoms at 10 years after index delivery (RR 13.3, 95% CI 3.9-33.1 and RR 14.1, 95% CI 2.5-18.8, respectively). Number of vaginal deliveries or other obstetric covariates did not affect the risk of stress urinary incontinence or urinary urgency. CONCLUSION: Vaginal delivery is independently associated with a significant long-term increase in stress urinary incontinence symptoms, as well as urinary urgency, regardless of maternal age or number of deliveries. LEVEL OF EVIDENCE: II-2.

Long-term outcome of abdominal sacrocolpopexy using xenograft compared with synthetic mesh.

OBJECTIVES: To assess the clinical outcome after abdominal sacrocolpopexy using a porcine dermal graft compared with a synthetic mesh. METHODS: Patients with vaginal vault prolapse Stage II or worse (Baden-Walker staging), underwent sacrocolpopexy using a synthetic mesh (n = 25) or porcine collagen graft (n = 27). The subjective outcome was measured using validated questionnaires. RESULTS: The mean clinical follow-up from surgery was 7.1 months for the xenograft compared with 7.4 months for the synthetic cohort. At clinical follow-up, vaginal vault prolapse Stage II was present in 8 (29%) of 27 patients in the xenograft cohort and 6 (24%) of 25 patients in the synthetic mesh cohort (no significant difference). The mean follow-up from surgery to survey was 2.5 years in the xenograft cohort and 4.3 years in the synthetic cohort. None of the patients in either cohort had undergone a secondary sacrocolpopexy. No significant differences were found between the cohorts regarding surgical morbidity other than more patients experiencing fever for 1 to 3 days in the xenograft cohort (P < 0.001). No significant differences were found in lower urinary tract symptoms, anorectal symptoms, or quality-of-life variables between the two cohorts. CONCLUSIONS: Abdominal sacrocolpopexy using a porcine dermal graft was comparable to synthetic mesh in terms of subjective and anatomic outcomes at mid to long-term follow-up.

A three-year prospective assessment of rectocele repair using porcine xenograft.

OBJECTIVE: To prospectively evaluate clinical outcome of rectocele repair using xenograft 3 years after surgery. METHODS: Twenty-three patients who completed evaluation preoperatively and 1 year after surgery were assessed at a 3-year follow-up. Clinical examination was performed preoperatively, and at the 1- and 3-year follow-ups, with the pelvic organ prolapse quantification system. Symptom assessment was performed with a validated bowel function questionnaire including questions on sexual function. RESULTS: There were no graft-related complications during the 3 years following surgery. Preoperatively, all patients had stage II prolapse of the posterior vaginal wall and a rectocele verified at defecography. At the 1-year follow-up, 11 of 29 patients (38%) had rectocele of stage II or more, and 4 patients were reoperated. At 3-year follow-up 7 of 23 patients (30%) had rectocele of stage II or more. When including the 4 early anatomical recurrences, a total of 11 of 27 patients (41%) had rectocele of stage II or more at 3-year follow-up. Preoperatively, all patients reported varying degrees of rectal emptying difficulties and symptoms of bowel dysfunction. There was a significant decrease in rectal emptying difficulties (P < .01), sense of incomplete evacuation (P < .01), need for manually assisted defecation (P < .05), and symptoms of pelvic heaviness (P < .001) at the 3-year follow-up compared with preoperatively. Cure of rectal emptying difficulties was reported by fewer than 50% of patients. There were no significant changes in anal incontinence scores or symptoms of sexual dysfunction at the 3-year follow-up compared with preoperatively. CONCLUSION: Rectocele repair using porcine dermal graft was associated with an unsatisfactory anatomical cure rate and persistent bowel-emptying difficulties in the majority of patients 3 years postoperatively. LEVEL OF EVIDENCE: II-3.

Functional and anatomic outcome after transvaginal rectocele repair using collagen mesh: a prospective study.

PURPOSE: This study was designed to evaluate rectocele repair using collagen mesh. METHODS: 32 female patients underwent surgical repair using collagen mesh. Outcome was assessed in 29 patients and preoperative assessment included standardized questionnaire, clinical examination, and defecography. At the six-month follow-up, patients answered a standardized questionnaire and underwent clinical examination. At the 12-month follow-up, patients answered a standardized questionnaire, underwent clinical examination, and defecography. RESULTS: Preoperatively, 26 patients had a Stage II and 3 patients had a Stage III rectocele. At the 6-month follow-up, five patients had rectocele > or = Stage II (P < 0.001) and at the 12-month follow-up, seven patients had rectocele > or = Stage II (P < 0.001) at clinical examination. At the preoperative defecography, all patients presented a rectocele. At the 12-month defecography, 14 patients had no rectocele (P < 0.001) and 15 had a rectocele. At the six-month follow-up, there was a significant decrease in rectal emptying difficulties, need of digital support of the posterior vaginal wall at defecation, and defecation frequency. At the 12-month follow-up, symptom improvement remained, but was less pronounced. CONCLUSIONS: Rectocele repair using collagen mesh improved anatomic support, but there is a substantial risk for recurrence with unsatisfactory anatomic and functional outcome one year after surgery. Rectocele repair using mesh was not associated with an increased risk of dyspareunia. Rectocele repair using biomaterial mesh reinforcement needs further evaluation before adopted into clinical practice.

Anatomical outcome and quality of life following posterior vaginal wall prolapse repair using collagen xenograft.

The aim of this study was to evaluate quality of life, sexual function, and anatomical outcome after posterior vaginal wall prolapse repair using a collagen xenograft. Thirty-three patients were evaluated preoperatively and at 6 and 12 months follow-up (FU). Quality of life and sexual function were assessed using a self-reported questionnaire. Prolapse staging was performed using the pelvic organ prolapse quantification system (POPQ). Preoperatively 3 patients had stage I, 26 patients stage II, and 4 patients stage III prolapse of the posterior vaginal wall. Prolapse of the posterior vaginal wall > or = stage II was observed in 7 patients (21%) at the 6-month FU and in 13 patients (39%) at the 12-month FU. Mean point Bp was reduced from -1.1 preoperatively to -2.5 at 6 months FU (p < 0.01) and -1.8 at 12 months FU (p < 0.01). Previous abdominal surgery was associated with a less favorable anatomical outcome (odds ratio: 2.0, 95% confidence interval: 1.5-3.8). There were no significant changes in sexual function or dyspareunia during the 1-year FU. Preoperatively 76% of the patients reported a negative impact on quality of life as a result of genital prolapse. There was a significant improvement in several variables associated with quality of life at 6 and 12 months FU. Posterior vaginal wall prolapse repair using a collagen xenograft was associated with an unsatisfying anatomical outcome at 1-year FU although several quality of life-associated variables affecting psychosocial function were improved. Improvement was not restricted to postoperative restoration of vaginal topography, and previous surgery had a negative effect on anatomical outcome.

Assessment of posterior vaginal wall prolapse: comparison of physical findings to cystodefecoperitoneography.

The aim of the present study was to compare clinical and radiological findings when assessing posterior vaginal wall prolapse. Defecography can be used to complement the clinical evaluation in patients with posterior vaginal wall prolapse. Further development of the defecography technique, using contrast medium in the urinary bladder and intraperitoneally, have resulted in cystodefecoperitoneography (CDP). Thirty-eight women underwent clinical examination using the pelvic organ prolapse quantification system (POP-Q) followed by CDP. All patients answered a standardized bowel function questionnaire. Statistical analysis measuring correlation between POP-Q and CDP using Pearson's correlation coefficient (r) and Spearman's rank order correlation coefficient (rs) demonstrated a poor to moderate correlation, r=0.49 and rs=0.55. Although there was a strong association between large rectoceles (>3 cm) at CDP and symptoms of rectal emptying difficulties (p<0.001), severity and prevalence of bowel dysfunction showed poor coherence with clinical prolapse staging and findings at radiological imaging. Vaginal topography and POP-Q staging predict neither radiological size nor visceral involvement in posterior vaginal wall prolapse. Radiological evaluation may therefore be a useful complement in selected patients.

Anal incontinence after vaginal delivery: a five-year prospective cohort study.

OBJECTIVE: The long-term prevalence of anal incontinence after vaginal delivery is unknown. The aim of the present study was to evaluate the prevalence of anal incontinence in primiparous women 5 years after their first delivery and to evaluate the influence of subsequent childbirth. METHODS: A total of 349 nulliparous women were prospectively followed up with questionnaires before pregnancy, at 5 and 9 months, and 5 years after delivery. A total of 242 women completed all questionnaires. Women with sphincter tear at their first delivery were compared with women without such injury. Risk factors for development of anal incontinence were also analyzed. RESULTS: Anal incontinence increased significantly during the study period. Among women with sphincter tears, 44% reported anal incontinence at 9 months and 53% at 5 years (P = .002). Twenty-five percent of women without a sphincter tear reported anal incontinence at 9 months and 32% had symptoms at 5 years (P < .001). Risk factors for anal incontinence at 5 years were age (odds ratio [OR] 1.1; 95% confidence interval [CI] 1.0-1.2), sphincter tear (OR 2.3; 95% CI 1.1-5.0), and subsequent childbirth (OR 2.4; 95% CI 1.1-5.6). As a predictor of anal incontinence at 5 years after the first delivery, anal incontinence at both 5 months (OR 3.8; 95% CI 2.0-7.3) and 9 months (OR 4.3; 95% CI 2.2-8.2) was identified. Among women with symptoms, the majority had infrequent incontinence to flatus, whereas fecal incontinence was rare. CONCLUSION: Anal incontinence among primiparous women increases over time and is affected by further childbirth. Anal incontinence at 9 months postpartum is an important predictor of persisting symptoms.

Clinical and histological safety assessment of rectocele repair using collagen mesh.

AIM: To clinically and histologically evaluate inflammatory response following rectocele repair using porcine collagen mesh. METHODS: Seventeen patients underwent rectocele repair using porcine collagen mesh. Inflammatory response was assessed by clinical and histological inflammatory grading pre- and postoperatively. Postoperative body temperature, complications and hospital stay was compared with 15 patients undergoing posterior colporraphy. RESULTS: Postoperative clinical examination did not demonstrate any inflammatory reaction. There were no significant changes in fibroblast count (P = 0.43), connective tissue density grading (P = 0.54), macrophage count (P = 0.20), inflammatory cell count (P = 0.48), total cell count (P = 0.51), or inflammatory grading (P = 0.87) postoperatively compared with preoperative values. Body temperature was significantly elevated for both the study and control group, although higher for the study group, postoperatively day 1 (P < 0.001). There were no significant differences in hospital stay and postoperative complications. CONCLUSION: Porcine collagen mesh was not associated with an adverse inflammatory response at clinical or histological evaluation and appears to be a safe material when used for rectocele repair.

Effect of hysterectomy on bowel function.

PURPOSE: Hysterectomy is the most common major gynecologic procedure. Unwanted postoperative effects on bowel function are a topic of recent debate. The aim of the present study was to prospectively evaluate the influence of hysterectomy on bowel function. METHODS: One hundred and twenty consecutive patients undergoing hysterectomy for benign conditions answered a questionnaire covering bowel habits and symptoms preoperatively and at 6 and 12 months postoperatively. Forty-four patients underwent vaginal hysterectomy and 76 underwent abdominal hysterectomy. Concomitant bilateral salpingo-oopherectomy was performed in 17 patients. RESULTS: After abdominal hysterectomy, patients reported increased symptoms of gas incontinence, urge to defecate, and inability to distinguish between gas and feces ( P < 0.05). There was a tendency of increased fecal incontinence. Subgroup analysis indicated that concomitant bilateral salpingo-oopherectomy resulted in an increased risk of fecal incontinence. No significant changes were detected in symptoms associated with constipation. Mean defecation frequency increased and the frequency of pelvic heaviness symptoms was reduced. After vaginal hysterectomy, there was no increased frequency of incontinence or constipation symptoms. The frequency of pelvic heaviness symptoms was reduced. CONCLUSIONS: Patients undergoing abdominal hysterectomy may run an increased risk for developing mild to moderate anal incontinence postoperatively and this risk is increased by simultaneous bilateral salpingo-oopherectomy. An increased risk of anal incontience symptoms could not be identified in patients undergoing vaginal hysterectomy. Our study does not support the assumption that hysterectomy is associated with de novo or deteriorating constipation.

Diagnosis of cystocele--the correlation between clinical and radiological evaluation.

In patients with genital prolapse involving several compartments simultaneously, radiologic investigation can be used to complement the clinical assessment. Contrast medium in the urinary bladder enables visualization of the bladder base at cystodefecoperitoneography (CDP). The aim of the present study was to evaluate the correlation between clinical examination using the Pelvic Organ Prolapse Quantification system (POP-Q) and CDP. Thirty-three women underwent clinical assessment and CDP. Statistical analysis using Pearson's correlation coefficient ( r) demonstrated a wide variability between the current definition of cystocele at CDP and POP-Q ( r=0.67). An attempt to provide an alternative definition of cystocele at CDP had a similar outcome ( r=0.63). The present study demonstrates a moderate correlation between clinical and radiologic findings in patients with anterior vaginal wall prolapse. It does not support the use of bladder contrast at radiologic investigation in the routine preoperative assessment of patients with genital prolapse.

The impact of hysterectomy on lower urinary tract symptoms.

The aim of this study was to prospectively evaluate the effect of vaginal and abdominal hysterectomy on lower urinary tract symptoms. We interviewed 120 patients undergoing hysterectomy for benign conditions preoperatively using a standardized questionnaire. At 6.6 and 12.7 months, 119/120 and 115/120 patients completed the follow-up questionnaire. Forty-four patients underwent vaginal and 76 abdominal hysterectomy. At 6 months follow-up there was a decrease ( p<0.05) in symptoms of stress urinary incontinence in the abdominal cohort, but this did not remain at 12 months' follow-up. There were no significant changes in symptoms of stress urinary incontinence in the vaginal cohort at either 6 or 12 months' follow-up. Postoperative micturition frequency was reduced in both cohorts. No significant differences were found regarding symptoms of urge urinary incontinence, urge complaints or voiding difficulties. The present study does not support the assumption that abdominal or vaginal hysterectomy is associated with de novo or deteriorating symptoms of urinary incontinence.

Obstetric sphincter tears and anal incontinence: an observational follow-up study.

BACKGROUND: Persistent defects after primary sphincter repair and occult sphincter tears are common after vaginal deliveries. Anal incontinence may be associated with these morphological defects. MATERIAL AND METHODS: Forty-six primiparous women were evaluated with ultrasonography, manometry and electrophysiology. Twenty-four women had undergone primary repair of obstetric sphincter tears (sphincter group), 16 women had no clinical sphincter tear but developed anal incontinence postpartum (symptom group), and six were delivered by elective cesarean section (cesarean group). RESULTS: In the sphincter group, 50% had anal incontinence at follow-up. At ultrasonography, 70% had injuries anteriorly in the midanal canal. At manometry, 4% had decreased resting pressure and 50% decreased squeeze pressure. At electrophysiology, 19% had pathologic pudendal latency and 25% pathologic fiber density. In the symptom group, 44% had injuries anteriorly in the midanal canal at ultrasonography. At manometry, all women had normal resting pressure and 19% had a decreased squeeze pressure. At electrophysiology, 46% had pathologic pudendal latency and 29% pathologic fiber density. In the cesarean group, 33% had mild anal incontinence at follow-up. Ultrasonography and manometry were normal in all women. At electrophysiology, 33% had pathologic pudendal latency and 17% pathologic fiber density. CONCLUSION: Anal sphincter injuries at childbirth are often inadequately diagnosed and primary repair frequently results in persisting defects in the anal sphincter. Anatomic injuries to the anal sphincter play an important role in the development of anal incontinence after delivery, but a significant proportion of symptomatic women also demonstrate neurologic impairment at electrophysiologic testing.