Sexual, bladder and bowel function following different minimally invasive techniques of radical hysterectomy in patients with early-stage cervical cancer.

PURPOSE: Despite the establishment of radical surgery for therapy of cervical cancer, data on quality of life and patient-reported outcomes are scarce. The aim of this retrospective cohort study was to evaluate bladder, bowel and sexual function in women who underwent minimally invasive surgery for early-stage cervical cancer. METHODS: From 2007-2013, 261 women underwent laparoscopically assisted radical vaginal hysterectomy (LARVH = 45), vaginally assisted laparoscopic or robotic radical hysterectomy (VALRRH = 61) or laparoscopic total mesometrial resection (TMMR = 25) and 131 of them completed the validated German version of the Australian Pelvic Floor Questionnaire (PFQ). Results were compared with controls recruited from gynecological clinics (n = 24) and with urogynecological patients (n = 63). RESULTS: Groups were similar regarding age, BMI and parity. The TMMR group had significantly shorter median follow-up (16 months versus 70 and 36 months). Postoperatively, deterioration of bladder function was reported by 70%, 57% and 44% in the LARVH, VARRVH and TMMR groups, respectively (p = 0.734). Bowel function was significantly worse after TMMR with a higher deterioration rate in 72 versus 43% (LARVH) and 47% (VARRVH) with a correspondingly higher bowel dysfunction score of 2.9 versus 1.5 and 1.8, respectively and 1.8 in urogynaecological patients. Sexual dysfunction was common in all surgical groups. 38% considered their vagina too short which was significantly associated with deep dyspareunia. Compared with controls, surgical groups had significantly increased PFQ scores. CONCLUSION: Pelvic floor dysfunction commonly deteriorates and negatively impacts on quality of life after minimally invasive radical hysterectomy, especially bowel function after TMMR. Pelvic floor symptoms should routinely be addressed pre- and postoperatively.

Surgical management of pelvic organ prolapse.

Despite pelvic organ prolapse being a universal problem experienced in nearly 50% of parous women, the surgical management of vaginal prolapse remains an enigma to many, with wide variation in the rates and types of intervention performed. As part of the 6th International Consultation on Incontinence (ICI) our committee, charged with producing an evidence-based report on the surgical management of prolapse, produced a pathway for the surgical management of prolapse. The 2017 ICI surgical management of prolapse evidence-based pathway will be presented and summarized. Weaknesses of the data and pathway will be discussed and avenues for future research proposed.

Diagnosis and Therapy of Female Pelvic Organ Prolapse. Guideline of the DGGG, SGGG and OEGGG (S2e-Level, AWMF Registry Number 015/006, April 2016).

Aims: The aim was to establish an official interdisciplinary guideline, published and coordinated by the German Society of Gynecology and Obstetrics (DGGG). The guideline was developed for use in German-speaking countries. In addition to the Germany Society of Gynecology and Obstetrics, the guideline has also been approved by the Swiss Society of Gynecology and Obstetrics (SGGG) and the Austrian Society of Gynecology and Obstetrics (OEGGG). This is a guideline published and coordinated by the DGGG. The aim is to provide evidence-based recommendations obtained by evaluating the relevant literature for the diagnostic, conservative and surgical treatment of women with female pelvic organ prolapse with or without stress incontinence. Methods: We conducted a systematic review together with a synthesis of data and meta-analyses, where feasible. MEDLINE, Embase, Cinahl, Pedro and the Cochrane Register were searched for relevant articles. Reference lists were hand-searched, as were the abstracts of the Annual Meetings of the International Continence Society and the International Urogynecological Association. We included only abstracts of randomized controlled trials that were presented and discussed in podium sessions. We assessed original data on surgical procedures published since 2008 with a minimum follow-up time of at least 12 months. If the studies included descriptions of perioperative complications, this minimum follow-up period did not apply. Recommendations: The guideline encompasses recommendations for the diagnosis and treatment of female pelvic organ prolapse. Recommendations for anterior, posterior and apical pelvic organ prolapse with or without concomitant stress urinary incontinence, uterine preservation options, and the pros and cons of mesh placements during surgery for pelvic organ prolapse are presented. The recommendations are based on an extensive and systematic review and evaluation of the current literature and include the experiences and specific conditions in Germany, Austria and Switzerland.

[Validation of a pelvic floor questionnaire with improvement and satisfaction scales to assess symptom severity, bothersomeness and quality of life before and after pelvic floor therapy]. / Beckenboden-Fragebogen für Frauen. Validierung eines Instrumentes mit posttherapeutischem Modul zur Evaluation von Symptomen, Leidensdruck, Lebensqualität, Verbesserung und Zufriedenheit.

BACKGROUND: The aim of this study was to integrate and validate an additional post-treatment module including improvement and satisfaction scales to the validated German pelvic floor questionnaire. METHODS: The questionnaire contained the domains bladder, bowel prolapse, and sexual symptoms. It was completed by 55 patients before and after specific pelvic floor rehabilitation. A post-therapy module with improvement and satisfaction scales was integrated and tested psychometrically. RESULTS: Missing data did not exceed 4%. Improvement and satisfaction correlated significantly with bladder and bowel domain scores. Test-retest reliability showed moderate to good agreement. The questionnaire was sensitive to change with a large effect size. The improvement of bladder symptoms in 91% of the women correlated with the domain score. CONCLUSION: The validated German pelvic floor questionnaire including a post-treatment module assesses symptoms, improvement and satisfaction in a reliable and reproducible fashion.

Surgical management of pelvic organ prolapse in women: a short version Cochrane review.

BACKGROUND: Pelvic organ prolapse may occur in up to 50% of parous women. A variety of urinary, bowel and sexual symptoms may be associated with prolapse. OBJECTIVES: To determine the effects of the many different surgeries in the management of pelvic organ prolapse. SEARCH STRATEGY: We searched the Cochrane Incontinence Group Specialised Trials Register (searched 3 May 2006) and reference lists of relevant articles. We also contacted researchers in the field. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials that included surgical operations for pelvic organ prolapse. DATA COLLECTION AND ANALYSIS: Trials were assessed and data extracted independently by two reviewers. Six investigators were contacted for additional information with five responding. MAIN RESULTS: Twenty two randomised controlled trials were identified evaluating 2368 women. Abdominal sacral colpopexy was better than vaginal sacrospinous colpopexy in terms of a lower rate of recurrent vault prolapse (RR 0.23, 95% CI 0.07 to 0.77) and less dyspareunia (RR 0.39, 95% CI 0.18 to 0.86), but the trend towards a lower re-operation rate for prolapse following abdominal sacrocolpopexy was not statistically significant (RR 0.46, 95% CI 0.19 to 1.11). However, the vaginal sacrospinous colpopexy was quicker and cheaper to perform and women had an earlier return to activities of daily living. The data were too few to evaluate other clinical outcomes and adverse events. The three trials contributing to this comparison were clinically heterogeneous. For the anterior vaginal wall prolapse, standard anterior repair was associated with more recurrent cystoceles than when supplemented by polyglactin mesh inlay (RR 1.39, 95% CI 1.02 to 1.90) or porcine dermis mesh inlay (RR 2.72, 95% CI 1.20 to 6.14), but data on morbidity, other clinical outcomes and for other mesh or graft materials were too few for reliable comparisons. For posterior vaginal wall prolapse, the vaginal approach was associated with a lower rate of recurrent rectocele and/or enterocele than the transanal approach (RR 0.24, 95% CI 0.09 to 0.64), although there was a higher blood loss and postoperative narcotic use. However, data on the effect of surgery on bowel symptoms and the use of polyglactin mesh inlay or porcine small intestine graft inlay on the risk of recurrent rectocele were insufficient for meta-analysis.Meta-analysis on the impact of pelvic organ prolapse surgery on continence issues was limited and inconclusive, although about 10% of women developed new urinary symptoms after surgery. Although the addition of tension-free vaginal tape to endopelvic fascia plication (RR 5.5, 95% CI 1.36 to 22.32) and Burch colposuspension to abdominal sacrocolpopexy (RR 2.13, 95% CI 1.39 to 3.24) were followed by a lower risk of women developing new postoperative stress incontinence, but other outcomes, particularly economic, remain to be evaluated. AUTHORS' CONCLUSIONS: Abdominal sacrocolpopexy is associated with a lower rate of recurrent vault prolapse and dyspareunia than the vaginal sacrospinous colpopexy. These benefits must be balanced against a longer operating time, longer time to return to activities of daily living and increased cost of the abdominal approach. The use of mesh or graft inlays at the time of anterior vaginal wall repair may reduce the risk of recurrent cystocele. Posterior vaginal wall repair may be better than transanal repair in the management of rectoceles in terms of recurrence of prolapse. The addition of a continence procedure to a prolapse repair operation may reduce the incidence of postoperative urinary incontinence but this benefit needs to be balanced against possible differences in costs and adverse effects. Adequately powered randomised controlled clinical trials are urgently needed.

Surgical management of pelvic organ prolapse in women.

BACKGROUND: Pelvic organ prolapse may occur in up to 50% of parous women. A variety of urinary, bowel and sexual symptoms may be associated with prolapse. OBJECTIVES: To determine the effects of the many different surgeries in the management of pelvic organ prolapse. SEARCH STRATEGY: We searched the Cochrane Incontinence Group Specialised Trials Register (searched 3 May 2006) and reference lists of relevant articles. We also contacted researchers in the field. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials that included surgical operations for pelvic organ prolapse. DATA COLLECTION AND ANALYSIS: Trials were assessed and data extracted independently by two reviewers. Six investigators were contacted for additional information with five responding. MAIN RESULTS: Twenty two randomised controlled trials were identified evaluating 2368 women. Abdominal sacral colpopexy was better than vaginal sacrospinous colpopexy in terms of a lower rate of recurrent vault prolapse (RR 0.23, 95% CI 0.07 to 0.77) and less dyspareunia (RR 0.39, 95% CI 0.18 to 0.86), but the trend towards a lower re-operation rate for prolapse following abdominal sacrocolpopexy was not statistically significant (RR 0.46, 95% CI 0.19 to 1.11). However, the vaginal sacrospinous colpopexy was quicker and cheaper to perform and women had an earlier return to activities of daily living. The data were too few to evaluate other clinical outcomes and adverse events. The three trials contributing to this comparison were clinically heterogeneous. For the anterior vaginal wall prolapse, standard anterior repair was associated with more recurrent cystoceles than when supplemented by polyglactin mesh inlay (RR 1.39, 95% CI 1.02 to 1.90) or porcine dermis mesh inlay (RR 2.72, 95% CI 1.20 to 6.14), but data on morbidity, other clinical outcomes and for other mesh or graft materials were too few for reliable comparisons. For posterior vaginal wall prolapse, the vaginal approach was associated with a lower rate of recurrent rectocele and/or enterocele than the transanal approach (RR 0.24, 95% CI 0.09 to 0.64), although there was a higher blood loss and postoperative narcotic use. However, data on the effect of surgery on bowel symptoms and the use of polyglactin mesh inlay or porcine small intestine graft inlay on the risk of recurrent rectocele were insufficient for meta-analysis.Meta-analysis on the impact of pelvic organ prolapse surgery on continence issues was limited and inconclusive, although about 10% of women developed new urinary symptoms after surgery. Although the addition of tension-free vaginal tape to endopelvic fascia plication (RR 5.5, 95% CI 1.36 to 22.32) and Burch colposuspension to abdominal sacrocolpopexy (RR 2.13, 95% CI 1.39 to 3.24) were followed by a lower risk of women developing new postoperative stress incontinence, but other outcomes, particularly economic, remain to be evaluated. AUTHORS' CONCLUSIONS: Abdominal sacrocolpopexy is associated with a lower rate of recurrent vault prolapse and dyspareunia than the vaginal sacrospinous colpopexy. These benefits must be balanced against a longer operating time, longer time to return to activities of daily living and increased cost of the abdominal approach. The use of mesh or graft inlays at the time of anterior vaginal wall repair may reduce the risk of recurrent cystocele. Posterior vaginal wall repair may be better than transanal repair in the management of rectoceles in terms of recurrence of prolapse. The addition of a continence procedure to a prolapse repair operation may reduce the incidence of postoperative urinary incontinence but this benefit needs to be balanced against possible differences in costs and adverse effects. Adequately powered randomised controlled clinical trials are urgently needed.

Surgical management of pelvic organ prolapse in women.

BACKGROUND: Pelvic organ prolapse may occur in up to 50% of parous women. A variety of urinary, bowel and sexual symptoms may be associated with prolapse. OBJECTIVES: To determine the effects of surgery in the management of pelvic organ prolapse. SEARCH STRATEGY: We searched the Cochrane Incontinence Group trials register (8 June 2004) and reference lists of relevant articles. We also contacted researchers in the field. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials that included surgical operations for pelvic organ prolapse. DATA COLLECTION AND ANALYSIS: Trials were assessed and data extracted independently by at least two reviewers. Four investigators were contacted for additional information with two responding. MAIN RESULTS: Fourteen randomised controlled trials were identified evaluating 1004 women. Abdominal sacral colpopexy was better than vaginal sacrospinous colpopexy in terms of a lower rate of recurrent vault prolapse (RR 0.23, 95% CI 0.07 to 0.77) and less dyspareunia (RR 0.39, 95% CI 0.18 to 0.86), but the trend towards a lower re-operation rate for prolapse following abdominal sacrocolpopexy was not statistically significant (RR 0.46, 95% CI 0.19 to 1.11). However, the vaginal sacrospinous colpopexy was quicker and cheaper to perform and women had an earlier return to activities of daily living. The data were to evaluate other clinical outcomes and adverse events. For the anterior vaginal wall prolapse, standard anterior repair was associated with more recurrent cystoceles than when supplemented by Vicryl mesh overlay (RR 1.39, 95% CI 1.02 to 1.90) but data on morbidity and other clinical outcomes were too few for reliable comparisons. For posterior vaginal wall prolapse, the vaginal approach was associated with a lower rate of recurrent rectocele and/or enterocele than the transanal approach (RR 0.24, 95% CI 0.09 to 0.64), although there was a higher blood loss and postoperative narcotic use. However, data on the effect of surgery on bowel symptoms and the use of polyglactin mesh overlay on the risk of recurrent rectocele were insufficient for meta-analysis.Meta-analysis on the impact of pelvic organ prolapse surgery on continence issues was limited and inconclusive, although about 10% of women developed new symptoms after surgery. However, more women with occult stress urinary incontinence developed postoperative stress urinary incontinence after endopelvic fascia plication alone than after endopelvic fascia plication and tension-free vaginal tape (RR 5.5, 95% CI 1.36 to 22.32). REVIEWERS' CONCLUSIONS: Abdominal sacrocolpopexy is associated with a lower rate of recurrent vault prolapse and dyspareunia than the vaginal sacrospinous colpopexy. These benefits must be balanced against a longer operating time, longer time to return to activities of daily living and increased cost of the abdominal approach. The use of a polyglactin mesh overlay at the time of anterior vaginal wall repair may reduce the risk of recurrent cystocele. Posterior vaginal wall repair may be better than transanal repair in the management of rectoceles in terms of recurrence of prolapse. Adequately powered randomised controlled clinical trials are urgently needed.

Pelvic floor dysfunction in women after pelvic trauma.

The aim was to assess symptoms of pelvic floor dysfunction in women following pelvic trauma. A retrospective questionnaire survey of 24 consecutive women was performed in a tertiary referral orthopaedic centre and urogynaecology unit. Sixteen women had a type B and eight a type C pelvic fracture (Association Osteosynthesis manual classification). The median age was 24 years (11-92). Twenty-one women were nulliparous. Sixteen women reported de novo pelvic floor dysfunction. Bladder symptoms occurred in 12, bowel problems in 11 and sexual dysfunction in 7 of 17 sexually active women. Pelvic fracture seems to be a risk factor for pelvic floor dysfunction.

Obstructed defecation caused by a cystourethrocele and mobile posterior vaginal wall: a case report.

Obstructed defecation may be caused by a rectocele and/or enterocele. Rectal wall procidentia may be due to an enterocele bulging into the rectum. Another cause of rectal procidentia resulting in obstructed defecation is presented. A 65-year-old woman complained of vaginal prolapse and incomplete bowel emptying. Pelvic examination revealed that a stage III anterior vaginal wall prolapse caused a mobile posterior vaginal wall to prolapse into the anal canal, resulting in rectal procidentia and subsequently in obstructed defecation. Careful assessment of all pelvic floor compartments is important to identify the cause of obstructed defecation, particularly in the absence of a rectocele.

Abdominal sacrocolpopexy and anatomy and function of the posterior compartment.

OBJECTIVE: To assess the effect of abdominal sacrocolpopexy with obliteration of the pouch of Douglas on anatomy and function of the posterior compartment. METHODS: We prospectively studied 33 consecutive women with pelvic organ prolapse who had abdominal sacrocolpopexies [expanded polytetrafluoroethylene (Gore-Tex)] with pouch of Douglas obliterations and posterior extensions of mesh, using a standardized questionnaire, urodynamic studies, pelvic floor fluoroscopies, and vaginal-rectal examinations (Baden-Walker classification). Concomitant colpoperineorrhaphy was done if rectoceles remained at rectovaginal examination at the end of sacrocolpopexy. The goal was to correct rectoceles transabdominally. RESULTS: Thirty-one women returned for follow-up investigations after 12--48 months (mean 26 months). Mean age was 61 years (range 41--77 years). There was no recurrence of vaginal vault prolapse, enterocele, or anterior rectal wall prolapse. Among 28 preoperative rectoceles, 16 recurred (57%) and one occurred de novo. Defecation problems (outlet constipation) were present in 21 women (64%) preoperatively and persisted or were altered in 12 (57%) after sacrocolpopexy. Grade of rectocele was associated significantly with symptoms of outlet constipation preoperatively, but not postoperatively (P =.002). CONCLUSION: Abdominal sacrocolpopexy with obliteration of the pouch of Douglas and posterior extension of the mesh was effective for vaginal vault prolapse, enterocele, and anterior rectal wall procidentia, but not concomitant rectocele. Twenty-eight percent of women described altered defecation with stool stopping higher in the rectosigmoid colon ("high outlet constipation"), which might have been caused by denervation during rectal mobilization.

The depth of the pouch of Douglas in nulliparous and parous women without genital prolapse and in patients with genital prolapse.

OBJECTIVES: This study was undertaken to assess the depth of the pouch of Douglas among nulliparous women and to compare it with those among parous women and patients with genital prolapse. STUDY DESIGN: The depth of the pouch of Douglas was measured in 22 nulliparous women and 28 parous women without genital prolapse and in 18 patients with prolapse of the posterior vaginal wall. RESULTS: The pouch of Douglas extended from 11% to 89% of the total vaginal length among nulliparous and parous women, without significant difference between these groups (mean, 49% and 45%, respectively). It was significantly deeper in patients with prolapse, ranging from 25% to 96% (mean, 72%). CONCLUSION: There is an extensive variation in the depth of the pouch of Douglas. A deep pouch of Douglas is frequently present in young nulliparous women and may increase the risk for development of a posterior vaginal wall prolapse.

Can uroflowmetry patterns in women be reliably interpreted?

Our aim was to investigate the proposition that uroflowmetry patterns can be reliably interpreted and correspond with specific urodynamic diagnoses. Uroflowmetry traces from 129 women with diagnoses of either genuine stress incontinence or detrusor instability were interpreted by four physicians with a minimum of 6 months experience in urogynecology. To test intraobserver variability, the traces were classified a second time 8 weeks later. Inter- and intraobserver variability was calculated by kappa analysis. There was marked intra- and interobserver variability in classification of traces, but no evidence of a correlation between urodynamic diagnosis and uroflowmetry pattern. Neither peak flow, total voided volume nor rate of acceleration of flow correlated with diagnosis. Although flow rates are important in predicting possible problems following surgery for stress incontinence, there is no evidence that flow patterns can be used as a screening test for specific urodynamic diagnoses.

Postpartum pelvic floor conditioning using vaginal cones: not only for prophylaxis against urinary incontinence and descensus.

Seventy-one women were examined 6-8 weeks after spontaneous delivery by pelvic floor (PF) palpation, inspection, manometry and gravimetry. Re-examination was performed in the same way after 4-6 weeks of daily cone training. Control groups included 20 women prior to and after conventional puerperal exercises, and 8 nulliparae prior to and after the same cone training, using a five-cone set. The number of puerperae not capable of voluntary PF contraction declined from 34% before to 6% after training. Optimum initial and post-training responses were exhibited by all nulliparae. Differences between cone and conventional exercise groups were of minor importance. Contractility increased from 5 to 10 mmHg on average in puerperae and from 15 mmHg to 21 mmHg in nulliparae. Cone nos. 1-3 were most frequently required at the beginning of training, and nos. 3-5 towards the end. Cone training works well as an alternative or complement to conventional postpartum exercises, and may therefore be recommended especially to puerperae who are not capable of holding vaginal cones of 20-70 g 6 weeks after delivery.

[Pelvic floor conditioning with vaginal weights--post partum and in urinary incontinence]. / Beckenbodenkonditionierung mit Vaginalgewichten -- post partum und bei Harninkontinenz.

To check on the efficacy of cone training 71 women were thoroughly examined six to eight weeks after spontaneous deliveries at various risk levels. Their pelvic floor was examined by palpation, inspection, manometry and gravimetry. All of them were re-examined in the same way after four to six weeks of daily cone training. Thirty women with moderate genuine stress incontinence (16) or stress/urge incontinence (14) were evaluated by the same procedure, independent of gestation. A control group included 20 women prior to and after conventional puerperal pelvic floor exercises and eight nulliparae of the same age prior to and after the same cone training, using a five-cone set. The number of puerperae not capable of voluntary pelvic floor contraction declined from 34 % before to 6 % after training. Optimum initial and posttraining responses, on the other hand, were exhibited by all nulliparae. Differences in childbirth risk for pelvic floor damage played a less important role than childbirth proper. Training related differences were of minor importance, as well, between cone and conventional exercise groups. Notwithstanding different initial values, all puerperae increased their contractility to 10 mm Hg on average, while the increase accomplished by nulliparae was from 15 mm Hg to 21 mm Hg. Cone Nos. 1-3 (20.0-45.0g) were most frequently required at the beginning of training and Nos. 3-5 (45.0-70.0 g) towards the end, for an average increase by one or two cone numbers. 25 % of the cone women and 35 % of the conventional exercise probands failed to complete the training, which was indicative of limited patient compliance after delivery. A positive correlation was found to exist between motivation and training success. Cone training also had positive effects on sexuality. It has proved to work well alternatively or complementary to conventional postpartum exercises and, therefore, may be recommended to all women who are not capable of holding with their pelvic floor vaginal cones of 20-70 g in the postpartum period. In women with urinary incontinence (UI) no pelvic floor response was recordable, prior to training, from five women (17 %). Response was not even recorded from eight women (21 %) by palpation. After training, the capability of voluntary and reflex contraction of pelvic floor muscles was restored in all women. The best post-training result was obtained from palpation (27 positive responses). Manometry and capability of the pelvic floor to hold vaginal cones were other suitable methods in this context: in 15 women (50 %) cone weights were extremely low at the beginning of treatment (Cone no. 1-2), while after treatment 19 women (63 %) held cones up to Nos. 4-5. All healthy women of the control group started with Cone No. 5. In conformity with postpartum groups average increase in pelvic floor contractility was from 5 mm to 10 mm Hg in UI patients. Twenty-four women (80 %) were cured from UI (57 %) or were improved (23 %). Twenty-six women asked for continuation of cone training. Pelvic floor conditioning, using vaginal cones, is a good alternative to poor acceptance or insufficient availability of conventional pelvic floor exercises in conservative treatment of urinary incontinence and descensus.

Vitamin A in parenteral nutrition: uptake and distribution of retinyl esters after intravenous application.

Short-term parenteral application of vitamin A was examined in rats. Retinyl margarinate, which is chemically similar to physiological retinyl esters, was used in vitamin A-depleted rats to study uptake, distribution, and storage of retinyl esters in tissues. Vitamin A-depleted and Vitamin A-sufficient rats were infused with a micellar suspension of retinyl margarinate for 7 h and then killed at different times. Retinyl margarinate was directly taken up by all tissues examined. It appears that infusion of retinyl esters in micellar form provides a direct way to supply vitamin A to peripheral, vitamin A-dependent tissues. Therefore, a short-term infusion of retinyl esters with an emulsifier may be an effective means of preventing development of vitamin A-deficiency during long-term application of TPN, particularly in cases of liver dysfunction.

Glucose uptake, lactate release, ketone body turnover, metabolic micromilieu, and pH distributions in human breast cancer xenografts in nude rats.

Glucose uptake, lactate release, ketone body utilization, spatial distribution of glucose, lactate, and ATP concentrations as well as tissue pH distributions were systematically investigated in s.c. and/or "tissue-isolated" human breast cancer xenografts in T-cell-deficient rnu/rnu rats. Large variations in all parameters were detected within and between tumors indicating a very nonuniform substrate turnover. Glucose was taken up by all xenografts. Glucose consumption rates increased with increasing glucose availabilities, implying that the glucose uptake is mainly determined by the efficiency of nutritive tumor blood flow. The average glucose uptake was 0.37 mumol/g/min in medullary and 0.26 mumol/g/min in squamous cell carcinomas of the breast. At wet weights below 5 g, medullary breast cancers consumed more glucose than squamous cell carcinomas (2P less than 0.05). Most tumors (97%) released lactate in an amount linearly related to glucose consumption. The lactate production of medullary (0.33 mumol/g/min) and squamous cell (0.31 mumol/g/min) breast cancers was similar. In general, the xenografts utilized ketone bodies. beta-Hydroxybutyrate was consumed by 82% and acetoacetate by 73% of the tumors, the uptake rates being linearly related to the respective availabilities. The mean uptake of beta-hydroxybutyrate was 3.48 nmol/g/min and that of acetoacetate 2.56 nmol/g/min. No significant differences were seen between medullary and squamous cell breast cancers. The beta-hydroxybutyrate/acetoacetate ratio in the tumor-venous blood rose with decreasing tumor blood flow indicating the development of hypoxia at advanced growth stages. Glucose, lactate, and ATP levels were all very heterogeneously distributed in medullary and squamous cell tumors as compared with normal tissue. No relationship was evident between the spatial distribution of concentrations of these three substrates. The xenografts were acidotic compared with pH values in normal subcutis. The mean tissue pH in medullary breast cancers was 6.81 +/- 0.25 (SD). Compared with these values, the tissue pH distribution in squamous cell breast cancers was shifted to significantly higher values. The mean pH of the latter tumors was 7.04 +/- 0.19 (2P less than 0.001). From the experimental data presented there is clear indication that the metabolism of the xenografts investigated was mainly determined by the efficiency of nutritive blood flow, i.e., by substrate availability, and not by the metabolic demand of the cancer cells.