Surgery for Gastrointestinal Stromal Tumors of the Stomach

Background  Gastrointestinal stromal tumors (GISTs) are the main mesenchymal neoplasms in the gastrointestinal tract. Tumor size, mitotic rate, and location correlate with potential malignancy and recurrence rate. Results of surgical treatment of gastric GIST are analyzed with emphasis on recurrence of disease after intermediate follow-up. Methods  From 1998 to 2006, a total of 63 patients (median age 62.1 ± 14.1) underwent gastric resection for GIST. Fifty-five patients (93.6%) returned for follow-up investigations, which included computed tomography in 45, gastroscopy in 32, and endosonography in 29. Positron emission tomography was done in five patients. Results  Mean tumor size was 5.3 ± 3.8 cm. Open atypical gastric resection was done in 32, distal gastric resection in five, and remnant gastrectomy in four patients. Laparoscopic gastric resection was initiated in 22 patients; the conversion rate was four of 22 (18.2%). Overall, R0 resection was reached in 61/63 patients (96.8%). According to the Fletcher criteria, 33 tumors (52.4%) were classified as intermediate or high risk GIST. Six patients (9.5%) died of unrelated causes before follow-up. After a median follow-up of 2.5 years, overall recurrence rate was 7.0% after R0 resection. Conclusion  Histologically proven complete resection is an effective treatment for gastric GIST. Laparoscopic procedures were carried out successfully in selected patients. Preliminary data were presented at the annual meeting of the European Association of Endoscopic Surgeons, Berlin 2006. No research grants funded this study.     

War Experiences and General Health Among People in Bosnia‐Herzegovina and Kosovo

War experiences may have an extensive impact on the health status of the exposed populations. This population‐based study aimed to examine the relationship between war experiences and self‐reported general health in representative sample surveys from Bosnia‐Herzegovina (n = 3,313) and Kosovo (n = 1,000). Data were collected with face‐to‐face interviews fielded in the winter of 2003–2004. Logistic regression analysis was used to compute unadjusted and adjusted odds ratios (ORs). The adjusted effects of the extensiveness of war experiences on poor health were positive in both countries, but they were statistically significant only for Bosnia‐Herzegovina: OR = 1.04, 95% CI [1.00, 1.08] for Bosnia‐Herzegovina and OR = 1.03, 95% CI [0.98, 1.09] for Kosovo. The strongest observed effect was found for Kosovo only: The extensiveness of war experiences was relatively strongly related to longstanding health problems, OR = 1.09, 95% CI [1.03, 1.15]. We found that war experiences may contribute to increased poorer health in the exposed populations; however, the effects 4–9 years after the war ended were modest. Hence, war experiences seemed to be more strongly related to war‐related distress and posttraumatic stress disorder than to self‐reported general health.     

Good outcome after liver transplantation for ALD without a 6 months abstinence rule prior to transplantation including post‐transplant CDT monitoring for alcohol relapse assessment – a retrospective study

Alcoholic liver disease (ALD) is the second most common indication for liver transplantation (LT). The utility of fixed intervals of abstinence prior to listing is still a matter of discussion. Furthermore, post‐LT long‐term observation is challenging, and biomarkers as carbohydrate‐deficient transferrin (CDT) may help to identify alcohol relapse. We retrospectively analyzed data from patients receiving LT for ALD from 1996 to 2012. A defined period of alcohol abstinence prior to listing was not a precondition, and abstinence was evaluated using structured psychological interviews. A total of 382 patients received LT for ALD as main (n = 290) or secondary (n = 92) indication; median follow‐up was 73 months (0–213). One‐ and five‐year patient survival and graft survival rates were 82% and 69%, and 80% and 67%, respectively. A total of 62 patients (16%) experienced alcohol relapse. Alcohol relapse did not have a statistically significant effect on patient survival (P = 0.10). Post‐transplant CDT measurements showed a sensitivity and specificity of 84% and 85%, respectively. In conclusion, this large single‐center analysis showed good post‐transplant long‐term results in patients with ALD when applying structured psychological interviews before listing. Relapse rates were lower than those reported in the literature despite using a strict definition of alcohol relapse. Furthermore, post‐LT CDT measurement proved to be a useful supplementary tool for detecting alcohol relapse.     

Treatment of painful vertebral fractures by kyphoplasty in patients with primary osteoporosis: a prospective nonrandomized controlled study.

This study investigates the effects of kyphoplasty on pain and mobility in patients with osteoporosis and painful vertebral fractures compared with conventional medical management. INTRODUCTION: Pharmacological treatment of patients with primary osteoporosis does not prevent pain and impaired activity of patients with painful vertebral fractures. Therefore, we evaluated the clinical outcome after kyphoplasty in patients with vertebral fractures and associated chronic pain for >12 months. MATERIALS AND METHODS: Sixty patients with primary osteoporosis and painful vertebral fractures presenting for >12 months were included in this prospective, nonrandomized controlled study. Twenty-four hours before performing kyphoplasty, the patients self-determined their inclusion into the kyphoplasty or control group so that 40 patients were treated with kyphoplasty, whereas 20 served as controls. This study assessed changes in radiomorphology, pain visual analog scale (VAS) score, daily activities (European Vertebral Osteoporosis Study [EVOS] score), number of new vertebral fractures, and health care use. Outcomes were assessed before treatment and at 3 and 6 months of follow-up. All patients received standard medical treatment (1g calcium, 1000 IE vitamin D(3), standard dose of oral aminobisphosphonate, pain medication, physical therapy). RESULTS: Kyphoplasty increased midline vertebral height of the treated vertebral bodies by 12.1%, whereas in the control group, vertebral height decreased by 8.2% (p = 0.001). Augmentation and internal stabilization by kyphoplasty resulted in a reduction of back pain. VAS pain scores improved in the kyphoplasty group from 26.2 +/- 2 to 44.2 +/- 3.3 (SD; p = 0.007) and in the control group from 33.6 +/- 4.1 to 35.6 +/- 4.1 (not significant), whereas the EVOS score increased in the kyphoplasty group from 43.8 +/- 2.4 to 54.5 +/- 2.7 (p = 0.031) and in the control group from 39.8 +/- 4.5 to 43.8 +/- 4.6 (not significant). The number of back pain-related doctor visits within the 6-month follow-up period decreased significantly after kyphoplasty compared with controls: mean of 3.3 visits/patient in the kyphoplasty group and a mean of 8.6 visits/patient in the control group (p = 0.0147). CONCLUSIONS: The results of this study show significantly increased vertebral height, reduced pain, and improved mobility in patients after kyphoplasty. Kyphoplasty performed in appropriately selected osteoporotic patients with painful vertebral fractures is a promising addition to current medical treatment.     

The multiply injured child

The treatment of multiple traumas in children requires knowledge of common injury patterns, incidence, mortality, and the consequences and differences between these injuries in children and adult patients. However, epidemiological studies concerning pediatric multiple trauma are rare. To address this, data were collected and analyzed from 682 multiple trauma patients treated at a Level I trauma center. The patients were divided into four age-related groups (< 6 years, 6-12 years, 13-18 years, and 18-40 years) and were evaluated for trauma mechanism, injury distribution, and cause of death. Children aged 6 to 17 years mostly were injured as pedestrians and cyclists whereas infants, preschoolers, and adults more commonly were injured as car passengers. Pediatric patients suffered a significantly higher mortality than adults, with a threefold increased risk of death when injured as passengers in car accidents. Injuries to the head and the legs were most common. A lower incidence of thoracic (28% versus. 62%), abdominal (20% versus 36%), pelvic (22% versus 35%), and upper limb (32% versus 43%) trauma was observed in children (< 18 years) than in adults (18-40 years). Nevertheless, trauma to the thorax, abdomen, and head were associated with a high risk of death in all groups. Spinal cord injuries, especially in the cervical region, also carried a high risk of mortality (36.8 in the group of patients younger than 18 years and 18.9 in the group of patients 18-40 years). Children younger than 6 years had the most severe head injuries. The data show that there are important differences in incidence, mortality, and injury patterns between pediatric and adult patients with multiple traumas.     

NEPH2 is located at the glomerular slit diaphragm, interacts with nephrin and is cleaved from podocytes by metalloproteinases

The NEPH family comprises three transmembrane proteins of the Ig superfamily interacting with the glomerular slit diaphragm proteins podocin and ZO-1. NEPH1 binds to nephrin, another component of the slit diaphragm, and loss of either partner causes heavy proteinuria. NEPH2, which is strongly conserved among a large number of species, is also expressed in the kidney; however, its function is unknown. The authors raised NEPH2 antisera to demonstrate NEPH2 expression in a variety of mouse tissues, including the kidney and a podocyte cell line. The authors localized the expression of NEPH2 to the glomerular slit diaphragm by electron microscopy and show NEPH2 homodimerization and specific interactions with the extracellular domain of nephrin in vitro and in vivo. NEPH1, however, failed to interact with NEPH2. The authors detected immunoreactive NEPH2 in urine of healthy subjects, suggesting that the extracellular domain is cleaved under physiologic conditions. These findings were confirmed in vitro in podocyte cell culture. Shedding is increased by tyrosine phosphatase inhibitors and diminished by GM6001, an inhibitor of metalloproteinases. Overexpression experiments indicate an involvement of the MT1-matrix metalloproteinase. The results suggest a role for NEPH2 in the organization and/or maintenance of the glomerular slit diaphragm that may differ from the functions of NEPH1 and nephrin.     

The efficacy of dietary intervention on urinary risk factors for stone formation in recurrent calcium oxalate stone patients

PURPOSE: Nutrition is suggested to be the major environmental risk factor in idiopathic calcium oxalate stone disease. The study was designed to evaluate the effect of dietary intervention on urinary risk factors for recurrence in calcium oxalate stone formers. MATERIALS AND METHODS: A total of 76 men and 31 women with idiopathic calcium oxalate stone disease collected 24-hour urine on their habitual, self-selected diets and after 7 days on a balanced standardized diet according to the recommendations for calcium oxalate stone formers. RESULTS: On the usual diet, a urine volume of less than 2.0 l per 24 hours was present in 57.9%, hypercalciuria in 25.2%, hypomagnesuria in 18.7%, hyperoxaluria in 14.0%, hyperuricosuria in 41.3% and hypocitraturia in 57.0% of patients. The frequency of metabolic abnormalities and the risk of calcium oxalate stone formation decreased significantly on the ingestion of the balanced diet, due to the significant increase in urinary volume, pH and citrate excretion and the significant decrease in urinary calcium and uric acid excretion. No change occurred in urinary oxalate and magnesium excretion. CONCLUSIONS: The evaluation of urinary risk profiles of the patients on their usual dietary habits revealed a high risk for calcium oxalate stone formation. A low fluid intake and an increased intake of protein and alcohol were identified as the most important dietary risk factors. The shift to a nutritionally balanced diet according to the recommendations for calcium oxalate stone formers significantly reduced the stone forming potential.     

Are therapeutic effects of antiacne agents mediated by activation of FoxO1 and inhibition of mTORC1?

Acne pathogenesis has recently been linked to decreased nuclear FoxO1 levels and increased mTORC1 activity. This hypothesis postulates that antiacne agents either enhance nuclear FoxO activity or inhibit mTORC1. Benzoyl peroxide (BPO), by activation of oxidative stress‐inducible kinases, increases nuclear FoxO levels promoting Sestrin3‐mediated AMPK activation. Furthermore, BPO‐derived ROS may activate AMPK via ataxia–telangiectasia mutated. Isotretinoin and all‐trans retinoic acid may stimulate FoxO gene expression. Doxycycline may enhance FoxOs nuclear retention by inhibiting the expression of exportin 1. Suppression of TNFα signalling by tetracyclines, erythromycin and other macrolides may attenuate IKKβ‐TSC1‐mediated mTORC1 activation. Erythromycin attenuates ERK1/2 activity and thereby increases TSC2. Azelaic acid may decrease mTORC1 by inhibiting mitochondrial respiration, increasing cellular ROS and nuclear FoxO levels. Antiandrogens may attenuate mTORC1 by suppressing mTORC2‐mediated Akt/TSC2 signalling. This hypothesis unmasks a common mode of action of antiacne agents as either FoxO enhancers or mTORC1 inhibitors and thus provides a rational approach for the development of new antiacne agents.