A 10-year follow up of reproductive function in women treated for childhood cancer

Previously, this study group found that female childhood cancer survivors could be at risk of early cessation of fertility. The aim of the present study was to evaluate reproductive function in the same group of survivors 10 years after the initial study. Of the original cohort of 100, 71 were re-examined. Thirty-six survivors reported regular menstrual cycles. When they were compared with 210 controls, they differed significantly in antral follicle count (AFC) (median 15 versus 18, P = 0.047) but not in anti-Müllerian hormone (AMH) (median 13.0 versus 17.8 pmol/l). Survivors cured with minimal gonadotoxic treatment had significantly higher AMH and AFC compared with survivors cured with either potentially gonadotoxic treatment or treatment including alkylating chemotherapy and ovarian irradiation (20.0, 5.8 and <3 pmol/l, P < 0.001; and 15, 9 and 2, P = 0.03, respectively). Thirty-eight survivors had achieved at least one live birth. Complicated second-trimester abortions (n = 4) were observed primarily in survivors cured with radiotherapy affecting pelvic organs. In conclusion, childhood cancer survivors have signs of diminished ovarian reserve. However, if the ovarian function is preserved in the early to mid-twenties, it is likely to persist until the mid-thirties, giving a good chance of childbearing.In this 10-year follow-up study, we report the reproductive function in adult female childhood cancer survivors. A total of 71 survivors out of an original cohort of 100 were re-examined in the present study. Thirty-six (51%) survivors reported regular menstrual cycles, six (8%) had irregular cycles, 11 (15%) used oral contraceptives, 12 (17%) used hormone replacement therapy and six (8%) were pregnant. When survivors with regular menstrual cycles (n = 36) were compared with control subjects (n = 210), there were only discrete signs of diminished reproductive function in the survivors. It is important to note, however, that reproductive function was compromised in survivors who had received antineoplastic treatment harmful to the ovaries. Among the 71 participating survivors 65% have been pregnant and 69% of the pregnancies have resulted in live births. Thus, the majority of the survivors, who had an apparently normal ovarian function in their mid-twenties, have conceived and delivered, and their ovarian reserve seems almost unchanged during the follow-up period. However, it should be highlighted that complicated second-trimester abortions (n = 4) were observed primarily in survivors cured with radiotherapy affecting pelvic organs.     

Photodynamic therapy with BF-200 ALA for the treatment of actinic keratosis: results of a multicentre, randomized, observer-blind phase III study in comparison with a registered methyl-5-aminolaevulinate cream and placebo

Background Photodynamic therapy (PDT) with 5‐aminolaevulinic acid (ALA) or its methylester [methyl‐5‐aminolaevulinate (MAL) or 5‐amino‐4‐oxopentanoate] was recently ranked as first‐line therapy for the treatment of actinic keratosis (AK) and is an accepted therapeutic option for the treatment of neoplastic skin diseases. BF‐200 ALA (Biofrontera Bioscience GmbH, Leverkusen, Germany) is a gel formulation of ALA with nanoemulsion for the treatment of AK which overcomes previous problems of ALA instability and improves skin penetration. Objectives To evaluate the efficacy and safety of PDT of AKs with BF‐200 ALA in comparison with a registered MAL cream and with placebo. Methods The study was performed as a randomized, multicentre, observer‐blind, placebo‐controlled, interindividual trial with BF‐200 ALA, a registered MAL cream and placebo in a ratio of 3 : 3 : 1. Six hundred patients, each with four to eight mild to moderate AK lesions on the face and/or the bald scalp, were enrolled in 26 study centres in Germany, Austria and Switzerland. Patients received one PDT. If residual lesions remained at 3 months after treatment, PDT was repeated. Results PDT with BF‐200 ALA was superior to placebo PDT with respect to patient complete clearance rate (78·2% vs. 17·1%; P < 0·0001) and lesion complete clearance rate (90·4% vs. 37·1%) at 3 months after the last PDT. Moreover, superiority was demonstrated over the MAL cream regarding the primary endpoint patient complete clearance (78·2% vs. 64·2%; P < 0·05). Significant differences in the patient and lesion complete clearance rates and severity of treatment‐related adverse events were observed for the narrow‐ and broad‐spectrum light sources. Conclusions BF‐200 ALA is a very effective, well‐tolerated new formulation for AK treatment with PDT and is superior to a registered MAL medication. Efficacies and adverse events vary greatly with the different light sources used.     

Isolated intradural lumbosacral tailgut cyst with carcinoid features

Tailgut cysts are developmental cysts that arise from remnants of the embryonic postanal gut and are typically located within the presacral, retrorectal space. Isolated cases of aberrant locations, including prerectal, perirenal, perianal, retrovesical, and subcutaneous locations, have been reported. Malignant transformations with the presence of adenocarcinomas or carcinoids have been recognized within these entities. It is well recognized that anterior sacrococcygeal abnormalities are present and are frequently caused by the slow-growing nature of the tailgut cysts and related mass effect; however, the authors are aware of no reports in the literature of isolated tailgut cysts within the thecal sac in direct contact with neural elements, without extension into the peritoneal cavity. In this case, a 28-year-old woman presented with progressive back pain, frequent urinary tract infections, and bowel dysfunction. She was found to have a purely intradural tailgut cyst with malignant transformation consistent with carcinoid. No peritoneal extension of her disease was found. The authors hypothesize that this is a rare developmental aberration that has not been commonly recognized and potentially has implications for embryological development.     

Transvaginal cholecystectomy is associated with reduced pain and decreased analgetic requirements compared to laparoscopic cholecystectomy

BACKGROUND: Natural orifice transluminal endoscopic surgery (NOTES) is regarded as less invasive than laparoscopic surgery. However, the assumed advantages of NOTES – such as reduced pain and faster recovery of patients should be verified. METHODS: In this prospective controlled study 30 women undergoing transvaginal cholecystectomy (TV-ChE) were compared with 30 women undergoing conventional laparoscopic cholecystectomy (LAP-ChE). RESULTS: Compared to the LAP-ChE group, the women of the TV-ChE group reported less postoperative pain and less analgesic consumption. Both the duration of stay in the recovery room and the hospital stay were shorter in the TV-ChE group. After a follow-up of 3 months none of the patients of the TV-ChE group complained of dyspareunia or other colpotomy-related complications. CONCLUSIONS: TV-ChE is a safe and less invasive surgical technique. Compared to LAP-ChE there are some advantages such as less need for analgesics, faster mobilization, more comfortable recovery and shorter hospital stay.     

Living-donor kidney transplantation: risks of the donor – benefits of the recipient

Abstract:  For patients with end-stage renal disease, kidney transplantation is the optimal therapy. Due to organ shortage, however, most patients have to wait on dialysis for a considerable period of time prior to transplantation. Living-donor kidney transplantation is a valid option to expand the organ pool and to reduce waiting time. The risk–benefit ratio of living-donor kidney transplantation needs to be evaluated critically, as healthy persons voluntarily donate an organ for transplantation. The available data from the literature seem to prove that the donor operation can be performed with a minimal perioperative risk. Regarding the long-term course after kidney donation, the published data suggest that the risk is minimal for well-selected healthy donors who are closely followed postoperatively. The potential donor, however, needs to be completely informed regarding the potential short- and long-term risks of kidney donation prior to the planned procedure. From the recipient point of view, transplantation of a kidney from a living donor is a very good if not the optimal option, as the short- and long-term outcomes seem to be favorable compared with cadaveric kidney transplantation. With donor safety being constantly monitored, it seems to be justified to further pursue living-donor kidney transplantation programs.     

RAGE Deficiency Improves Postinjury Sciatic Nerve Regeneration in Type 1 Diabetic Mice

Peripheral neuropathy and insensate limbs and digits cause significant morbidity in diabetic individuals. Previous studies showed that deletion of the receptor for advanced end-glycation products (RAGE) in mice was protective in long-term diabetic neuropathy. Here, we tested the hypothesis that RAGE suppresses effective axonal regeneration in superimposed acute peripheral nerve injury attributable to tissue-damaging inflammatory responses. We report that deletion of RAGE, particularly in diabetic mice, resulted in significantly higher myelinated fiber densities and conduction velocities consequent to acute sciatic nerve crush compared with wild-type control animals. Consistent with key roles for RAGE-dependent inflammation, reconstitution of diabetic wild-type mice with RAGE-null versus wild-type bone marrow resulted in significantly improved axonal regeneration and restoration of function. Diabetic RAGE-null mice displayed higher numbers of invading macrophages in the nerve segments postcrush compared with wild-type animals, and these macrophages in diabetic RAGE-null mice displayed greater M2 polarization. In vitro, treatment of wild-type bone marrow–derived macrophages with advanced glycation end products (AGEs), which accumulate in diabetic nerve tissue, increased M1 and decreased M2 gene expression in a RAGE-dependent manner. Blockade of RAGE may be beneficial in the acute complications of diabetic neuropathy, at least in part, via upregulation of regeneration signals.Diabetes leads to the development of multiple complications (1–3). Peripheral neuropathy affects 30–50% of all diabetic patients (4–6). Individuals with diabetes are more vulnerable to superimposed thermal and pressure injuries (7–10). Diabetic individuals exposed to either topical application of capsaicin or intracutaneous excision axotomy (punch skin biopsy) displayed a reduction in regenerative rate, even without evidence of neuropathy, and reduced axonal regenerative sprouting and blood vessel growth, respectively, compared with nondiabetic control subjects (11,12). Studies of diabetic animals reported a delay of axonal regeneration after acute sciatic nerve crush compared with nondiabetic mice (13). Evidence suggests that enhanced accumulation of advanced glycation end products (AGEs) may be an important contributing mechanism to the pathogenesis of diabetes complications (14,15). AGEs are a heterogeneous group of molecules that impact cellular properties and gene expression via specific receptors such as receptor for advanced end-glycation product (RAGE) (16–18). RAGE, a pattern recognition receptor, also interacts with multiple members of the proinflammatory S100/calgranulin family and with high-mobility group box 1 protein (HMGB1); both classes of molecules are implicated in inflammation and cellular migration (19,20). These non-AGE ligands may be released by dying cells, and evidence suggests that although RAGE is not intimately involved in innate immune responses, its upregulation and activation by these ligands contribute to sustained inflammation and suppression of repair (21,22).These considerations prompted us to hypothesize that RAGE action in superimposed acute injury to the peripheral nerve, particularly in diabetes, attenuates neurite outgrowth and axonal regeneration via tissue-damaging inflammatory mechanisms. We subjected wild-type (WT) and homozygous RAGE-null mice to acute sciatic nerve crush to dissect the specific contribution of bone marrow RAGE expression. We also subjected WT mice to lethal irradiation and performed reconstitution with bone marrow expressing or devoid of RAGE.     

Identifying Change Targets for Posttraumatic Stress Disorder Among Suicidal and Self-Injuring Women With Borderline Personality Disorder

Research on psychotherapies for posttraumatic stress disorder (PTSD) is increasingly focused on understanding not only which treatments work but why and for whom they work. The present pilot study evaluated the temporal relations between five hypothesized change targets—posttraumatic cognitions, guilt, shame, general emotion dysregulation, and experiential avoidance—and PTSD severity among women with PTSD, borderline personality disorder, and recent suicidal and/or self-injurious behaviors. Participants (N = 26) were randomized to receive 1 year of dialectical behavior therapy (DBT) with or without the DBT prolonged exposure (DBT PE) protocol for PTSD. Potential change targets and PTSD were assessed at 4-month intervals during treatment and at 3-month posttreatment follow-up. Time-lagged mixed-effects models indicated that between-person differences in all change targets except guilt were associated with more severe PTSD, η²s = .32–.55, and, except for general emotion dysregulation, slowed the rate of change in PTSD severity over time, η²s = .20–.39. In DBT but not in DBT + DBT PE, individuals with higher levels of guilt and experiential avoidance relative to their own average had more severe PTSD at the next assessment point, η²s = .12–.25. The associations between the proposed change targets and PTSD severity were not bidirectional, except for general emotion dysregulation, η² = .50; and posttraumatic cognitions, η² = .06. These preliminary findings suggest that trauma-related cognitions, shame, and guilt, as well as problems regulating them, may be important change targets for improving PTSD in this patient population.     

Kyphoplastie in Kombination mit intraoperativer Radiotherapie

Background

Operative and radiotherapeutic procedures are available for the treatment of symptomatic vertebral metastases. The method for treatment of vertebral metastases presented in this article involves a combination of intraoperative radiotherapy (IORT) and kyphoplasty.

Methods and results

Kyphoplasty-IORT allows treatment of symptomatic vertebral metastases between vertebrae T3 and L5. With the patient under intubation narcosis an extrapedicular or bipedicular access to the vertebra is selected as for conventional kyphoplasty. This is followed by insertion of special sheaths of the radiation applicator and radiation therapy is intraoperatively administered via a radiation generator (Intrabeam®, Carl Zeiss Surgical, Oberkochen, Germany). The radiation dose is 8 Gy at a depth of 5–10 mm depending on the study protocol (50 kV X-radiation). Following radiation a conventional kyphoplasty procedure (Medtronic, USA) is carried out and the vertebra stabilized with cement.

Conclusions

The procedure presented demonstrates a new approach to treatment of vertebral metastases and represents a valuable alternative to previously established methods.     

Anesthetic management of patients with ornithine transcarbamylase deficiency

Ornithine transcarbamylase deficiency (OTCD) is the most common inborn error of the urea cycle. Several specific factors require care during anesthesia in patients with this condition to avoid metabolic decompensation with acute hyperammonemia and encephalopathy. We report monozygous twins with severe neonatal-onset OTCD undergoing general anesthesia twice each, with midazolam, s-ketamine, fentanyl and isoflurane in combination with surgical field infiltration with ropivacaine. Alternative pathway medication and high-caloric diet with 10% glucose solutions were continuously administered during the perioperative course. Both children were extubated within 10 min of the final suture, and their neurological state remained unchanged. Perioperatively, blood ammonia levels remained within the normal range.