Inkeri Schultz

Melanoma-educated CD14+ cells acquire a myeloid-derived suppressor cell phenotype through COX-2-dependent mechanisms.

Tumors can suppress the host immune system by employing a variety of cellular immune modulators, such as regulatory T cells, tumor-associated macrophages, and myeloid-derived suppressor cells (MDSC). In the peripheral blood of patients with advanced stage melanoma, there is an accumulation of CD14(+)HLA-DR(lo/-) MDSC that suppress autologous T cells ex vivo in a STAT-3-dependent manner. However, a precise mechanistic basis underlying this effect is unclear, particularly with regard to whether the MDSC induction mechanism relies on cell-cell contact of melanoma cells with CD14(+) cells. Here, we show that early-passage human melanoma cells induce phenotypic changes in CD14(+) monocytes, leading them to resemble MDSCs characterized in patients with advanced stage melanoma. These MDSC-like cells potently suppress autologous T-cell proliferation and IFN-γ production. Notably, induction of myeloid-suppressive functions requires contact or close proximity between monocytes and tumor cells. Further, this induction is largely dependent on production of cyclooxygenase-2 (COX-2) because its inhibition in these MDSC-like cells limits their ability to suppress T-cell function. We confirmed our findings with CD14(+) cells isolated from patients with advanced stage melanoma, which inhibited autologous T cells in a manner relying up prostaglandin E2 (PGE2), STAT-3, and superoxide. Indeed, PGE2 was sufficient to confer to monocytes the ability to suppress proliferation and IFN-γ production by autologous T cells ex vivo. In summary, our results reveal how immune suppression by MDSC can be initiated in the tumor microenvironment of human melanoma.

Long-term results and functional outcome after Ripstein rectopexy

PURPOSE: The aim of this study was to evaluate operative mortality, morbidity, and functional results after Ripstein rectopexy for rectal prolapse and internal rectal intussusception. METHODS: Sixty-nine patients with rectal prolapse and 43 with internal rectal intussusception were included. All patient records were studied and complications registered. Long-term follow-up was possible in 105 patients and performed by clinical examination and standardized interview, telephone interview, or patient records. Seventy-six patients were prospectively evaluated, comparing bowel function before and after rectopexy. RESULTS: There was no operative mortality. Operative morbidity was 33 percent, and most complications were minor. Severe early complications included one large-bowel obstruction and one transient ureteric stenosis. Median time of follow-up was seven years in patients with rectal prolapse and 5.4 years in patients with internal rectal intussusception. Late complications included two rectovaginal fistulas and one lethal sigmoid fecaloma. Five patients underwent subtotal colectomy for severe constipation. There was one recurrent prolapse (1.6 percent). Functional evaluation showed that incontinence improved (P=0.049), whereas the number of bowel movements per week decreased (P<0.001). Frequency of emptying difficulties did not change significantly in patients with rectal prolapse but increased in patients with internal rectal intussusception (P=0.038). CONCLUSION: Ripstein rectopexy can be performed with low mortality and recurrence rate, but with a high early complication rate. There were also some serious late complications. Continence was improved, although increased constipation was a problem in some patients, especially among those with internal rectal intussusception.

Delayed shoulder exercises in reducing seroma frequency after modified radical mastectomy: A prospective randomized study

AbstractBackground: Seromas and impaired shoulder function are well-known complications after modified radical mastectomy for breast cancer. Early postoperative physiotherapy is a common treatment to avoid shoulder dysfunction. The aim of this study was to evaluate if the frequency of postoperative seromas could be reduced, without increasing shoulder dysfunction, by delayed postoperative shoulder exercises. Methods: In a prospective study 163 patients with breast cancer undergoing modified radical mastectomy were randomized to physiotherapy starting on postoperative day 1 or day 7. Patients were seen by the surgeons and the physiotherapists during hospital stay and in the outpatient department. Seromas and other complications were registered by the surgeons. The physiotherapists instructed the patients pre- and postoperatively and assessed shoulder function. Results: There was a significantly higher incidence of postoperative seromas in the group of patients that started physiotherapy postoperative day 1 (38%) compared to the group that started physiotherapy postoperative day 7 (22%) (p<0.05). There was no significant difference between the groups in the late outcome of shoulder function. Conclusion: The incidence of seromas after modified radical mastectomy for breast cancer is reduced by delaying shoulder exercises one week postoperatively. Earlier postoperative physiotherapy is not necessary to avoid impaired shoulder function.

Influence of electrical and thermal properties on RF ablation of breast cancer: is the tumour preferentially heated?

BackgroundTechniques based on radio frequency (RF) energy have many applications in medicine, in particular tumour ablation. Today, mammography screening detects many breast cancers at an early stage, facilitating treatment by minimally invasive techniques such as radio frequency ablation (RFA). The breast cancer is mostly surrounded by fat, which during RFA-treatment could result in preferential heating of the tumour due to the substantial differences in electrical parameters. The object of this study was to investigate if this preferential heating existed during experimental in vitro protocols and during computer simulations.MethodsExcised breast material from four patients with morphologically diagnosed breast cancers were treated with our newly developed RFA equipment. Subsequently, two finite element method (FEM) models were developed; one with only fat and one with fat and an incorporated breast cancer of varying size. The FEM models were solved using temperature dependent electrical conductivity versus constant conductivity, and transient versus steady-state analyses.ResultsOur experimental study performed on excised breast tissue showed a preferential heating of the tumour, even if associated with long tumour strands. The fat between these tumour strands was surprisingly unaffected. Furthermore, the computer simulations demonstrated that the difference in electrical and thermal parameters between fat and tumour tissue can cause preferential heating of the tumour. The specific absorption rate (SAR) distribution changed significantly when a tumour was present in fatty tissue. The degree of preferential heating depended on tissue properties, tumour shape, and placement relative to the electrode. Temperature dependent electrical conductivity increased the thermal lesion volume, but did not change the preferential heating. Transient solutions decreased the thermal lesion volume but increased the preferential heating of the tumour.ConclusionBoth the computer model and the in vitro study confirmed that preferential heating of the tumour during RFA exists in breast tissue. However, the observed preferential heating in the in vitro studies were more pronounced, indicating that additional effects other than the difference in tissue parameters might be involved. The existing septa layers between the cancer tissue and the fatty tissue could have an additional electrical or thermal insulating effect, explaining the discrepancy between the in vitro study and the computer model.

Continence is improved after the Ripstein rectopexy: Different mechanisms in rectal prolapse and rectal intussusception?

PURPOSE: This study was undertaken to evaluate anal manometric changes after Ripsteins operation for rectal prolapse and rectal intussusception and to study the clinical outcome following the operation, with special reference to anal incontinence. METHODS: Forty-two patients with rectal prolapse or rectal intussusception were subjected to anorectal manometry preoperatively and seven days and six months postoperatively. A detailed history was obtained from each patient preoperatively and six months postoperatively. RESULTS: Preoperatively, patients with rectal intussusception had higher maximum resting pressure (MRP) (52±23 mmHg) than patients with rectal prolapse (34±20 mmHg;P<0.01). In the group of patients with rectal prolapse, there was a postoperative increase in MRP after six months (P<0.001) but not after seven days. Maximum squeeze pressure (MSP) did not increase. Neither MRP nor MSP increased postoperatively in patients with internal rectal procidentia. Continence was improved postoperatively both in patients with rectal prolapse (P<0.01) and rectal intussusception (P<0.01). There was no postoperative increase in rectal emptying difficulties. CONCLUSION: Ripsteins operation often improved anal continence in patients with rectal prolapse and rectal intussusception. This improvement was accompanied by increased MRP in patients with rectal prolapse, indicating recovery of internal anal sphincter function. No postoperative increase in MRP was found in patients with rectal intussusception. This suggests an alternate mechanism of improvement in patients with rectal intussusception.

Pelvic Organ Prolapse and Urinary Incontinence in Women With Surgically Managed Rectal Prolapse: A Population-Based Case-Control Study

PurposeThis study aimed to investigate the prevalence of genital prolapse surgery and urinary incontinence in female patients operated on for rectal prolapse compared with a matched control group without rectal prolapse.MethodsFifty-two patients with a history of abdominal rectal prolapse surgery and 200 randomly selected age-matched and gender-matched control subjects without rectal prolapse received an extensive health care history survey.ResultsResponse rate in the patient group was 48 of 52 (92 percent) and 165 of 200 (82 percent) in the control group. Rectal prolapse was associated with an increased risk of surgery for uterine prolapse (odds ratio = 3.1; 95 percent confidence interval = 1.4–6.9) and vaginal wall prolapse (odds ratio = 3.2; 95 percent confidence interval = 1.3–7.8). Mean age at hysterectomy because of uterine prolapse was 54.7 years in the patient group compared with 62.6 years in the control group (P < 0.01). Mean age at vaginal wall prolapse surgery was 60.2 years in the patient group compared with 66.6 years in the control group (P < 0.05). There were no significant differences between the cohorts regarding prevalence or age at debut of urinary incontinence.ConclusionOur results indicate a strong association between rectal and genital prolapse surgery suggesting that diagnosis of rectal prolapse necessitating surgical intervention should prompt a multidisciplinary pelvic floor assessment.

Whole gut transit is prolonged after Ripstein rectopexy.

OBJECTIVE To find out if there are changes in transit time after Ripstein rectopexy and whether measurement of whole gut transit time preoperatively can predict postoperative constipation. DESIGN Prospective open study. SETTING Teaching hospital, Sweden. SUBJECTS 30 patients undergoing Ripstein rectopexy for rectal prolapse (n = 17) or internal rectal intussusception (n = 13). METHODS Whole-gut transit studies and recording of symptoms of constipation preoperatively and postoperatively. MAIN OUTCOME MEASURES Constipation and retention of markers. RESULTS Significantly more markers were retained in postoperative compared with preoperative transit studies (p < 0.001). Constipation mainly presented as emptying difficulties and there was no increase in the total number of patients who reported emptying difficulties postoperatively. There was a weak but significant correlation between retention of markers preoperatively and postoperative emptying difficulties (p < 0.05). CONCLUSION Whole gut transit was prolonged after Ripstein rectopexy. Preoperative retention of markers indicated an increased risk of postoperative constipation.

Preoperative electrophysiologic assessment cannot predict continence after rectopexy

PURPOSE: The aim of this study was to evaluate preoperative electrophysiologic assessment for prediction of anal continence after rectopexy. METHODS: Forty-three patients with rectal prolapse (n=26) or internal rectal intussusception (n=17) underwent concentric-needle electromyography, fiber density determination by single-fiber electromyography of the external anal sphincter, and pudendal nerve terminal motor latency evaluation before Ripstein rectopexy. A detailed history was obtained from each patient preoperatively and postoperatively. RESULTS: Anal continence was improved after rectopexy, both in patients with rectal prolapse (P=0.06) and in those with internal rectal intussusception (P=0.003). Abnormal results were registered in one or several aspects of the electrophysiologic assessment in 31 (72 percent) of the patients. However, functional outcome with respect to continence was not predicted by preoperative electromyography or pudendal nerve terminal motor latency assessment results. CONCLUSION: Electrophysiologic examinations in the preoperative assessment of patients with rectal prolapse and internal rectal intussusception do not predict continence after the Ripstein rectopexy. The routine use of electrophysiologic assessment requires further definition.

Paradoxical sphincter reaction is influenced by rectal filling volume

PURPOSE: Paradoxical sphincter reaction is frequently found in constipated patients but sometimes also in incontinent patients and in asymptomatic subjects. Its significance in defecation disorders has, therefore, been debated. The aim of the present study was to investigate whether paradoxical sphincter reaction is influenced by rectal filling volume. PATIENTS AND METHODS: Eighteen patients with defecation disorders and paradoxical sphincter reaction shown by electromyography were reinvestigated with an extended electromyographic investigation while in the lying position and while in the sitting position, with 50-ml, 100-ml, and 150-ml water-filled rectal balloons. RESULTS: All 18 patients showing paradoxical sphincter reaction in the first investigation also showed the reaction at the second investigation in the lying position with a 0-ml volume of rectal contents. In the sitting position, with a volume of 150 ml of rectal contents, the increase in electromyographic activity disappeared in seven patients (39 percent) and no longer showed paradoxical sphincter reaction. Electromyography showed decreased activity in one patient and unchanged activity in six patients during straining. A closing reflex was seen after completed straining in all of these seven patients. CONCLUSIONS: The present study demonstrates that paradoxical sphincter reaction diagnosed by electromyography is influenced by the rectal filling volume and might diminish when the rectum is filled with contents. The conventional electrophysiologic technique in the diagnosis of paradoxical sphincter reaction might, therefore, overdiagnose this condition.

Genitalprolaps und Harninkontinenz bei Frauen mit operativ behandeltem Rektumprolaps

ZusammenfassungFragestellung:Ziel dieser Studie war es, die Prävalenz von Genitalprolaps-Operationen und Harninkontinenz bei Patientinnen, die wegen eines Rektumprolaps operiert worden waren, im Vergleich zu einer entsprechenden Kontrollgruppe ohne Rektumprolaps zu untersuchen.Patienten und Methodik:52 Patientinnen mit Rektumprolaps-Operationen in der Vorgeschichte sowie 200 willkürlich ausgewählte, alters- und geschlechtsangepasste Kontrollpersonen ohne Rektumprolaps erhielten einen ausführlichen Gesundheitsfragebogen.Ergebnisse:Die Rücklaufquote betrug in der Patientinnengruppe 48 von 52 (92%) und in der Kontrollgruppe 165 von 200 (82%). Ein Rektumprolaps war mit einem gesteigerten Operationsrisiko wegen eines Uterusprolaps (Odds-Ratio = 3,1; 95%-Konfidenzintervall = 1,4–6,9) und eines Vaginalprolaps (Odds-Ratio = 3,2; 95%-Konfidenzintervall = 1,3–7,8) assoziiert. Das mittlere Alter bei einer Hysterektomie wegen Uterusprolaps betrug 54,7 Jahre in der Patientinnengruppe, verglichen mit 62,6 Jahren in der Kontrollgruppe (p < 0,01). Das mittlere Alter bei Vaginalprolaps-Operation betrug 60,2 Jahre in der Patientinnengruppe, verglichen mit 66,6 Jahren in der Kontrollgruppe (p < 0,05). Es fanden sich keine signifikanten Unterschiede zwischen den Gruppen bezüglich einer höheren Prävalenz oder des Alters beim ersten Auftreten einer Harninkontinenz.Schlussfolgerung:Die Ergebnisse zeigen einen starken Zusammenhang zwischen einer rektalen und genitalen Prolapsoperation. Dies legt nahe, dass der Diagnose eines Rektumprolaps, der operiert werden soll, eine multidisziplinäre Beckenboden-Untersuchung folgen muss.AbstractPurpose:This study aimed to investigate the prevalence of genital prolapse surgery and urinary incontinence in female patients operated on for rectal prolapse compared with a matched control group without rectal prolapse.Methods:Fifty-two patients with a history of abdominal rectal prolapse surgery and 200 randomly selected age- and gender-matched control subjects without rectal prolapse received an extensive health care history survey.Results:Response rate in the patient group was 48 of 52 (92 percent) and 165 of 200 (82 percent) in the control group. Rectal prolapse was associated with an increased risk of surgery for uterine prolapse (odds ratio = 3.1; 95 percent confidence interval = 1.4–6.9) and vaginal wall prolapse (odds ratio = 3.2; 95 percent confidence interval = 1.3–7.8). Mean age at hysterectomy because of uterine prolapse was 54.7 years in the patient group compared with 62.6 years in the control group (p < 0.01). Mean age at vaginal wall prolapse surgery was 60.2 years in the patient group compared with 66.6 years in the control group (p < 0.05). There were no significant differences between the cohorts regarding prevalence or age at debut of urinary incontinence.Conclusion:Our results indicate a strong association between rectal and genital prolapse surgery suggesting that diagnosis of rectal prolapse necessitating surgical intervention should prompt a multidisciplinary pelvic floor assessment.