A molecularly integrated grade for meningioma

BackgroundMeningiomas are the most common primary intracranial tumor in adults. Clinical care is currently guided by the World Health Organization (WHO) grade assigned to meningiomas, a 3-tiered grading system based on histopathology features, as well as extent of surgical resection. Clinical behavior, however, often fails to conform to the WHO grade. Additional prognostic information is needed to optimize patient management.MethodsWe evaluated whether chromosomal copy-number data improved prediction of time-to-recurrence for patients with meningioma who were treated with surgery, relative to the WHO schema. The models were developed using Cox proportional hazards, random survival forest, and gradient boosting in a discovery cohort of 527 meningioma patients and validated in 2 independent cohorts of 172 meningioma patients characterized by orthogonal genomic platforms.ResultsWe developed a 3-tiered grading scheme (Integrated Grades 1-3), which incorporated mitotic count and loss of chromosome 1p, 3p, 4, 6, 10, 14q, 18, 19, or CDKN2A. 32% of meningiomas reclassified to either a lower-risk or higher-risk Integrated Grade compared to their assigned WHO grade. The Integrated Grade more accurately identified meningioma patients at risk for recurrence, relative to the WHO grade, as determined by time-dependent area under the curve, average precision, and the Brier score.ConclusionWe propose a molecularly integrated grading scheme for meningiomas that significantly improves upon the current WHO grading system in prediction of progression-free survival. This framework can be broadly adopted by clinicians with relative ease using widely available genomic technologies and presents an advance in the care of meningioma patients.     

Biliary Sphincter of Oddi Dysfunction Type I Versus Occult Biliary Microlithiasis in Post-cholecystectomy Patients: Are They Both Part of the Same Clinical Entity?

We speculate that biliary sphincter of Oddi dysfunction type I and symptomatic migrating biliary microlithiasis may be part of the same disease process. A retrospective analysis of prospectively collected data was carried out using procedure and diagnosis codes during the period of 1997–2006. Seventeen patients (age 51 ± 17; 94% women) with prior cholecystectomy, right upper quadrant/epigastric abdominal pain, elevated liver enzymes, dilated biliary ducts seen on ultrasound/CT scan were identified. The patients underwent ERCP with biliary endoscopic sphincterotomy. Nine (53%) had biliary microlithiasis and eight (47%) had biliary sphincter of Oddi dysfunction type I. They were followed for 2–108 weeks (median 9 weeks). 6/8 (75%) in biliary sphincter of Oddi dysfunction type I and 6/9 (67%) in biliary microlithiasis group had resolution of abdominal pain (P = 1.00). We conclude that the clinical improvement with biliary sphincterotomy for biliary sphincter of Oddi dysfunction type I versus occult biliary microlithiasis was not significantly different.     

Negative muscle pennation angle as a sign of massive musculotendinous retraction after tendon tear: paradoxical function of the vastus lateralis muscle

Case report In the presented case, an isolated vastus lateralis tendon tear resulted in a negative pennation angle of the distal muscle fibers acting paradoxical to the physiological direction of the proximal muscle fibers. This observation makes the value of an in situ repair of a far retracted tendon tear with interposition of a graft questionable and emphasizes early over late anatomic surgical restoration of the muscle architecture after tendon tears.     

Waiting for radiation therapy: Does it matter?

The aim of this study was to determine the direct and indirect effects of prolonged waiting times for radiation therapy. We used the Medline, CancerNet and EMBASE databases to search the international research using the keywords radiotherapy, waiting times and delay. The negative effects of prolonged waiting times for radiation therapy can be broken down into direct and indirect effects. Direct effects include tumour control factors and patient factors. Indirect effects include changes in referral patterns and change in management of tumours. The precise effects of prolonged waiting times for radiation therapy are difficult to define. Evidence exists for some tumour sites, such as postoperative head and neck, small‐cell lung cancer and high‐grade cerebral gliomas, that tumour control might be adversely affected. The effect on other tumour sites is less established. Patient factors are likely to be consistent across all tumour types and indirect effects are hard to quantify.     

Use of a minimally invasive donor nephrectomy program to select technique for live donor nephrectomy

BACKGROUND: Live donor nephrectomy (LDN) is a major surgical procedure with an accepted low mortality and morbidity. Minimally invasive donor nephrectomy (MIDN) has been shown to decrease the wound morbidity associated with the lumbotomy of the classic open technique. Transplant programs face the challenge of initiating their MIDN programs without jeopardizing the safety of the donor and the graft quality. We present the experience at the University of Calgary after the initiation of a MIDN program, with a preoperative selective approach using the 3 major techniques for LDN. METHODS: From December 2001 to May 2004, 50 consecutive, accepted, live kidney donors were evaluated and chosen to undergo nephrectomy by an open, laparoscopic, or hand-assisted technique. Patients were chosen for a particular technique based on the criteria of vascular anatomy, size of abdominal cavity, previous surgery, and technical implications for the recipient. RESULTS: A total of 15 open, 11 laparoscopic, and 24 hand-assisted nephrectomies were performed. There were no statistically significant differences in sex, age, or body mass index between the groups. There were statistically significant differences in surgical times (P < .001) and in the number of days spent in the hospital (P < .001). All kidneys had primary function. There were 2 conversions in the hand-assisted group and 1 blood transfusion in the open group. Death-censored graft survival was 100% with an observation time of 20 months (SD +/- 9 months; range = 3-32 months). One graft from the hand-assisted group was lost from patient death with functioning graft 8 months after transplant. CONCLUSIONS: The learning curve for MIDN does not necessarily need to impact donor or recipient outcomes. The initiation of an MIDN program can be implemented safely if the cases are selected carefully and the use of the classic open technique is kept as an alternative.     

Bile Duct Injuries at Laparoscopic Cholecystectomy: A Single-Institution Prospective Study. Acute Cholecystitis Indicates an Increased Risk

During the last decade laparoscopic cholecystectomy (LC) has become established as the gold standard. The drawbacks in the form of bile duct (BD) injuries have also come into focus. We present the results of a prospective, consecutive series of 1568 patients with reference to BD injuries regarding risks, management, and preventive measures. The significant complications of all patients operated upon with LC between October 1999 and December 2003 were recorded prospectively. BD injuries were classified according to Strasberg into types A–E. Transected major BDs, injuries of type E, were regarded as “major” injuries and types A, B, C, and D were “minor” injuries. Major BDs were transected in five patients (0.3%), three of whom had acute cholecystitis. In the two patients operated on electively, the BD injuries were detected postoperatively, while they were detected intraoperatively when the operation was performed of necessity. The BDs were all reconstructed with a Roux-en-Y hepaticojejunostomy. Two patients had anastomotic strictures. Minor BD injuries were encountered in 19 patients (1.2%). The 13 patients with leakage from the cystic duct or gallbladder bed, injury type A, were treated by endoscopic (ERC) stenting without sequelae. Five patients sustained a lateral BD injury, type D; they were treated with a simple suture over a T-tube (at LC) or endoscopically (ERC) without further problems. A transected aberrant right hepatic BD, type C injury, was due to its small-caliber sutured. Minor BD injuries could be managed at the primary hospital if the endoscopic expertise were at hand. Acute cholecystitis seems to be a risk factor for BD injuries.     

Mechanisms underlying quercetin-induced vasorelaxation in aorta of subchronic diabetic rats: an in vitro study

In this study, the mechanisms involved in vasorelaxant effect of the flavonoid quercetin was investigated in isolated aortic rings from streptozotocin (STZ)-diabetic rats. After 4 weeks, addition of quercetin (0.1 microM-1 mM) caused a significant dose-dependent relaxation of noradrenaline (NA)- and KCl-preconstricted rings in both control and diabetic groups with a significant inter-group difference of P<0.01. Furthermore, both nitro-L-arginine-methyl ester (L-NAME, 100 microM) and indomethacin (10 microM) markedly attenuated the vasorelaxant responses following quercetin application. Meanwhile, endothelium removal significantly attenuated the quercetin-induced vasorelaxation. It is concluded that the quercetin can relax the preconstricted rings of aorta in subchronic STZ-diabetic rats through nitric oxide- and -prostaglandin-mediated pathways, which themselves could be considered as endothelium-dependent.     

Understanding the breast cancer experience of women: a qualitative study of African American, Asian American, Latina and Caucasian cancer survivors

Breast cancer is the most common form of cancer in American women across most ethnic groups. Although the psychosocial impact of breast cancer is being studied, there is little information on women from diverse ethnic and socioeconomic backgrounds. We conducted a qualitative study with breast cancer survivors (BCS) of various ethnicities. A total of 102 BCS participated in focus group interviews (24 African Americans, 34 Asians, 26 Latinas and 18 Caucasians); 20 health professionals participated in key informant interviews. Important ethnic differences in type of treatment were noted, Asians and Latinas were more likely to receive mastectomies and African American BCS were least likely to receive adjuvant therapies, including radiation and chemotherapy. These BCS enjoyed a fairly good overall health-related quality of life (HRQOL) with some persistent concerns. The prevailing concerns among all women included overall health, moderate physical concerns, cancer recurrence or metastases, psychosocial concerns related to worry about children and burdening the family, and body image and sexual health concerns. Additional challenges included: lack of knowledge about breast cancer; medical care issues such as insurance, cost and amount of time spent with physician; cultural sensitivity of providers, language barriers, cultural factors related to beliefs about illness, gender role and family obligations (e.g. self-sacrifice). These BCS, particularly the women of color, voiced that their spiritual beliefs and practices are central to their coping. This study accomplishes two goals; it adds to the sparse literature concerning the psychosocial sequelae of breast cancer among women of color, and it increases our knowledge of specific cultural influences (e.g. dietary practices, coping) and socio-ecological factors on HRQOL. More importantly, the study addressed areas that have not been studied before, specifically, an in-depth study on BCS QOL comparing multiple ethnic groups in the US. The results of this investigation will provide preliminary information to survivors and health-care providers about the impact of culture and socio-ecological contexts on survivorship. Among women of all major ethnic groups, breast cancer is the most common form of cancer and the second leading cause of cancer death (American Cancer Society (ACS), 2002). In 2002, over 203,000 women in the United States will be diagnosed with breast cancer (ACS, 2002). Ethnic disparities exist for cancer stage, diagnosis, survival, morbidity and mortality. In general, ethnic minority women are diagnosed with more advanced disease and experience greater morbidity and mortality (Haynes & Smedley, 1999; Miller et al., 1996; Ries et al., 2000; Shinagawa, 2000). In general, increases in survival rates have prompted greater interest in the quality of life (QOL) of breast cancer survivors (BCS) over the past two decades. Additionally, the QOL of cancer survivors from diverse ethnic, cultural and socioeconomic backgrounds is an emerging priority area for studies on survivorship research and clinical care (Haynes and Smedley, 1999; National Cancer Institute (NCI), 2002; President's Cancer Panel, 2000).     

New approach to polycystic ovary syndrome and other forms of anovulatory infertility

Anovulation can be classified in the clinic on the basis of serum hormone assays. Low gonadotropins along with low estrogen concentrations are suggestive of a central origin of the disease, whereas low estrogen levels along with elevated gonadotropins indicate a primary defect at the ovarian level. Most anovulatory patients (approximately 80%) present with serum FSH and estradiol levels within the normal range (World Health Organization class II). Polycystic ovary syndrome (PCOS) is a common but poorly defined heterogeneous clinical entity. Historically, characteristic ovarian abnormalities represented a hallmark of the syndrome. Because several etiological factors may lead to a similar end point (i.e., polycystic ovaries), the development of a clinically applicable classification of the syndrome has proven difficult. Clinical, morphological, biochemical, endocrine, and, more recently, molecular studies have identified an array of underlying abnormalities and added to the confusion concerning the pathophysiology of the disease. Despite the vast literature regarding the etiology and classification of PCOS, no consensus has been reached regarding the validity of criteria used to diagnose the syndrome. For instance, the significance of elevated serum luteinizing hormone (LH) concentrations, insulin resistance or polycystic-appearing ovaries assessed by ultrasound for PCOS diagnosis remains uncertain. In contrast, hyperandrogenism and chronic anovulation generally are believed to be mandatory diagnostic features. Patients with PCOS might visit a dermatologist for hirsutism, a generalist, or internist for complaints related to obesity or a gynecologist for irregular or absent bleeding. However, most patients seek the care of a gynecologist because of cycle abnormalities (oligomenorrhea) and infertility. In PCOS, serum FSH and estradiol (E2) levels are usually found to be within the (broad) normal ranges, whereas LH may either be normal or elevated. Because PCOS with normal or high LH does not seem to represent different clinical entities, it seems justifiable to consider this syndrome as a subgroup of WHO-II patients, although estrogen levels may be tonically elevated in these patients. This review will focus on characteristics of the heterogeneous group of WHO-II patients in an attempt to identify factors involved in the etiology and possible ovulation induction outcome of PCOS. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader will be able to outline the current classification of anovulatory infertility and to explain the characteristics and features used for classification.