ASGE guideline on the role of endoscopy in the management of benign and malignant gastroduodenal obstruction

This American Society for Gastrointestinal Endoscopy guideline provides evidence-based recommendations for the endoscopic management of gastric outlet obstruction (GOO). We applied the Grading of Recommendations, Assessment, Development and Evaluation methodology to address key clinical questions. These include the comparison of (1) surgical gastrojejunostomy to the placement of self-expandable metallic stents (SEMS) for malignant GOO, (2) covered versus uncovered SEMS for malignant GOO, and (3) endoscopic and surgical interventions for the management of benign GOO. Recommendations provided in this document were founded on the certainty of the evidence, balance of benefits and harms, considerations of patient and caregiver preferences, resource utilization, and cost-effectiveness.

Comparison of robotic-assisted and conventional laparoscopy in the management of adnexal masses.

STUDY OBJECTIVE: To compare the outcome of robotic-assisted laparoscopy vs conventional laparoscopy in the management of ovarian masses. DESIGN: Retrospective cohort (Canadian Task Force classification II-3). SETTING: Academic medical centre in the northeast United States. PATIENTS: Retrospective medical record review of 71 consecutive patients with presumed benign ovarian masses. INTERVENTION: Robotic-assisted laparoscopy in 30 patients with presumed benign ovarian masses was compared with conventional laparoscopy in 41 patients. MEASUREMENTS AND MAIN RESULTS: Operative outcomes including operative time, estimated blood loss, length of hospital stay, and complications were recorded. Standard statistical analysis was used to compare the outcomes in the 2 groups. Mean (SD) operative time in the robotic group was 1.95 (0.63) hours, which was significantly longer than in the conventional laparoscopic group, 1.28 (0.83) hours (p = .04). Estimated blood loss in the robotic group was 74.52 (56.23) mL, which was not significantly different from that in the conventional laparoscopic group, 55.97 (49.18) mL. There were no significant differences in length of hospital stay between the robotic and conventional laparoscopic groups: 1.20 (0.78) days and 1.48 (0.63). Conversion to laparotomy was not necessary in either group of patients. Intraoperative and postoperative complications were similar between the 2 groups. CONCLUSION: Robotic-assisted laparoscopy is a safe and efficient technique for management of various types of ovarian masses. However, conventional laparoscopy is preferred for management of ovarian masses because of shorter operative time. Prospective studies are needed to evaluate the outcomes of robotic-assisted laparoscopic management of benign and malignant ovarian neoplasms.

[Level of satisfaction in the emergency department. What about the residents?]. / Satisfaction aux urgences ou urgence de satisfaction. Qu'en est-il des assistants?

Emergency medicine is evolving within medical departments that are or will be experiencing major restructuring. The interdisciplinary organization of the emergency department (ED) is the result of a long reflexion from hospital managers or health professionals facing a real challenge: find an answer to the population's needs while providing a good and safe health system. For young residents, working in an interdisciplinary model implies to practice in an emerging specialty that they might not have chosen. Hence, there is no official assessment method allowing residents to give a feedback of their work in the ED. With this survey, we wanted to have the opinion and the feeling of young doctors that worked in such an interdisciplinary model.

[Sudden cardiac death: epidemiology and modern therapy]. / La mort subite: de l' épidémiologie à la prévention.

Sudden Cardiac Death (SCD) has become an important public health challenge in the Western World. In Switzerland near 10,000 people suffer each year from SCD. The survival from SCD to hospital discharge is discouraging (near 5%). Large majority of events occur unexpectedly in the out-of-hospital environment and are not predicted with great accuracy by risk profiling. Because the majority of SCD occur by the mechanism of ventricular fibrillation, community-based defibrillation strategies have emerged as one approach to SCD problem. Newer strategies of defibrillation designed to respond faster to out-of-hospital cardiac arrest, including public access defibrillation, as well as aggressive primary and secondary prevention of coronary artery disease appears as the best approach for successful management of SCD.

Impaired access of lymphocytes to neoplastic prostate tissue is associated with neoangiogenesis in the tumour site.

Recent reports demonstrated that neovasculature of certain murine tumours inhibits migration of lymphocytes to malignant tissues. We examined the possible existence of this phenomenon in human prostate adenocarcinoma by relating extent, patterns and composition of leucocyte infiltrates in adenocarcinoma specimens (N=28) to microvessel density and percentages of these vessels expressing adhesion molecules CD54, CD106 and CD62E. Specimens of nodular hyperplasia (N=30) were used as a control for nonmalignant prostate. Increased microvessel density was detected in foci of adenocarcinoma, as compared with adjacent benign areas (P=0.004) or hyperplastic specimens (P=0.001). Only CD54 was detected on prostate vasculature; percentages of CD54-expressing vessels in adenocarcinoma lesions and adjacent areas were higher than in hyperplasia (P=0.041 and P=0.014, respectively). Infiltrating leucocytes were either scattered diffusely in tissue or organised into clusters mainly composed of CD4-positive lymphocytes; smaller percentage of tissue was occupied by clustered infiltrates in adenocarcinoma foci (mean=0.7; median=0; range=0-5) than in adjacent tissue (mean=2.5; median=1; range=0-15; P=.021) and hyperplasia (mean=1.9; median=2; range=0-5; P=.006). In adenocarcinoma foci, microvessel density tended to negatively correlate with percentage of tissue occupied by an overall leucocyte infiltrate (mean=8.6; median=7.5; range=30) and negatively correlated with percentage of tissue occupied by clustered infiltrate (P=0.045). Percentage of CD54-expressing vessels positively correlated with percentage of tissue occupied by an overall (mean=12; median=10; range=30; P=0.01) and clustered (P=0.023) infiltrate in hyperplasia, whereas in carcinoma-adjacent benign areas, correlation was detected only for clustered infiltrates (P=0.02). The results indicate that impaired access of lymphocytes to malignant lesions is associated with increased numbers of newly formed blood vessels, whereas vascular CD54 likely contributes to extravasation of lymphocytes only in benign prostate tissue.

Age at first birth and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers.

An early age at first full-term birth is associated with a reduction in the subsequent development of breast cancer among women in the general population. A similar effect has not yet been reported among women who carry an inherited BRCA1 or BRCA2 mutation. We conducted a matched case-control study on 1816 pairs of women with a BRCA1 (n = 1405) or BRCA2 (n = 411) mutation in an attempt to elucidate the relationship between age at first full-term pregnancy and the risk of developing breast cancer. Information about the age at first childbirth and other pregnancy-related variables was derived from a questionnaire administered to women during the course of genetic counselling. There was no difference in the mean age at first full-term birth in the cases and controls (24.9 years vs. 24.8 years; P = 0.81, respectively). Compared to women whose first child was born at or before 18 years of age, a later age at first full-term birth did not influence the risk of developing breast cancer (OR = 1.00 per year; 95% CI 0.98-1.03; P-trend = 0.67). Stratification by mutation status did not affect the results. These findings suggest that an early first full-term birth does not confer protection against breast cancer in BRCA mutation carriers. Nonetheless, BRCA mutation carriers opting for a prophylactic oophorectomy as a breast and/or ovarian cancer risk-reducing strategy should complete childbearing prior to age 40 when this prevention modality is most effective.

The flow-cytometry-based evaluation of cellular immunity in cases of cutaneous leishmaniasis and healthy controls from the endemic area in southern Israel.

Only limited data are available on the early immunological events associated with human cutaneous leishmaniasis (CL). In this study, peripheral-blood mononuclear cells were obtained from 66 individuals (34 patients with cutaneous lesions and 32 apparently healthy controls) who had each spent no more than 3 months in the endemic region of Qetzioth, in southern Israel. These cells' responses to Leishmania major antigen were then explored, by the flow-cytometry-based evaluation of blast transformation (BT). The lymphocytes from 17 (50%) of the patients but only one (3%) of the controls displayed BT. When, in an ELISA, most (52) of the subjects were checked for anti-L. major antibodies, none of the 22 controls investigated but 19 (63%) of the 30 patients were found seropositive. Although 14 (47%) of the 30 patients who were checked for antibodies were BT-positive, the seropositive patients were not significantly more or less likely to be BT-positive than the seronegative patients (P<0.919). These data indicate that, in CL, the hosts' cellular and humoral responses develop independently within the first 3 months post-infection, but further investigation is required to confirm this hypothesis.

[Prehospital medical care organization during the 2003 G8 summit: a new concept of Mobile Medical Squadrons (MMS)]. / Organisation des secours extrahospitaliers lors du sommet 2003 du G8: nouveau concept de poste médical mobile (PMM).

OBJECTIVE: The occurrence of the 2003 G8 summit in Evian and the threat of major civil riots or even terrorist attacks in the Swiss neighbourhood forced us to imagine a new system of rescue and medical care in case of numerous victims. Previous occurrences of the G8 in Europe or America have demonstrated the need of flexible and mobile structures, able to respond quickly to crowd movements, unlike the usual static structure of rescue systems designed for major accidents. METHODS: We developed a new concept of Mobile Medical Squadrons (MMS) consisting of several vehicles and medical care and rescue human resources. In our concept, each MMS consisted of 3 emergency doctors, 5 paramedics and 9 first-aid workers. They were designed to handle 15 patients, with a large autonomy in terms of rescue, medical care, evacuation and medical authority. The equipment included medical, resuscitation, simple decontamination, evacuation and communication materials. RESULTS: The MMS were dispatched four times during the G8 summit following civil riots. They took care of 12 injured patients. CONCLUSION: The concept of MMS as a reinforcement of the existing rescue and health care resources appears as a new flexible, a modular and useful concept for the medical management of collective prehospital emergency situations. Its use is suggested instead of the traditional static concept of rescue systems designed for major accidents.

Low electric field enhanced chemotherapy can cure mice with CT-26 colon carcinoma and induce anti-tumour immunity.

Low electric field cancer treatment-enhanced chemotherapy (LEFCT-EC) is a new anticancer treatment which utilizes a combination of chemotherapeutic agents and a low electric field. We investigated the antitumour effectiveness of this technique in a model of murine colon carcinoma (CT-26). The low electric field was applied to approximately 65 mm3 intracutaneous tumours after intratumoral injection of 5FU, bleomycin or BCNU. We observed significant tumour size reduction and a prolongation of survival time. The complete cure of a significant fraction of animals treated by LEFCT-EC with 5FU (33%), bleomycin (51%) or BCNU (83%) was observed. Mice cured by LEFCT-EC developed resistance to a tumour challenge and their splenocytes had antitumour activity in vivo. Our results suggest that LEFCT-EC is an effective method for treatment of solid tumours.

The integrity of cholesterol-enriched microdomains is essential for the constitutive high activity of protein kinase B in tumour cells.

A deregulated activity of PKB/Akt (where PKB stands for protein kinase B) renders tumour cells resistant to a variety of apoptosis-inducing stimuli. Elucidation of the mechanisms responsible for this deregulation is of prime importance for the development of novel anti-cancer drugs. Results of the present study demonstrate that the constitutive activity of PKB/Akt in B16BL6 melanoma cells depends on the integrity of cholesterol-enriched membrane microdomains, since the exposure of cells to cholesterol-depleting agents decreases the phosphorylation of this enzyme, with no change in its total protein level. Inhibitors of Hsp90 (heat-shock protein 90) decreased phosphorylation of PKB/Akt with a similar pattern. Dephosphorylation of the enzyme, as a consequence of raft disintegration, could be precluded by inhibition of serine/threonine (but not tyrosine) phosphatases. Our results imply that destabilization of lipid rafts seemingly affects the association of Hsp90 with the respective serine/threonine phosphatases, thereby increasing the accessibility to PKB/Akt to deactivating phosphatases. We have found recently that reconstituted expression of H-2K class I glycoproteins in class I-deficient B16BL6 cells also decreases the phosphorylation of PKB/Akt. Therefore it is possible that raft-associated regulation of this important enzyme involves both H-2K glycoproteins and Hsp90.

Non-immune functions of MHC class I glycoproteins in normal and malignant cells.

MHC class I glycoproteins play a pivotal role in the regulation of immune responses by presenting antigenic peptides to cytotoxic T lymphocytes and by regulating cytolytic activities of natural killer cells. Cells originating in malignant tumours are often characterized by a profound immune escape phenotype. This phenotype is frequently associated with alterations in MHC class I-related antigen processing and presentation that enable tumours to escape immune surveillance. However, it now becomes clear that MHC class I molecules do not only provide a mechanistic framework for the presentation of antigenic peptides but, rather, possess broader biological functions due to their ability to regulate cell-to-cell communication and receptor-mediated trans-membrane signal transduction. In the present review we made an attempt to reevaluate the significance of an altered MHC class I phenotype for tumour progression in view of the current state of knowledge concerning the aforementioned non-immune functions performed by these membrane glycoproteins.

High-resolution serum proteomic features for ovarian cancer detection.

Serum proteomic pattern diagnostics is an emerging paradigm employing low-resolution mass spectrometry (MS) to generate a set of biomarker classifiers. In the present study, we utilized a well-controlled ovarian cancer serum study set to compare the sensitivity and specificity of serum proteomic diagnostic patterns acquired using a high-resolution versus a low-resolution MS platform. In blinded testing sets, the high-resolution mass spectral data contained multiple diagnostic signatures that were superior to the low-resolution spectra in terms of sensitivity and specificity (P<0.00001) throughout the range of modeling conditions. Four mass spectral feature set patterns acquired from data obtained exclusively with the high-resolution mass spectrometer were 100% specific and sensitive in their diagnosis of serum samples as being acquired from either unaffected patients or those suffering from ovarian cancer. Important to the future of proteomic pattern diagnostics is the ability to recognize inferior spectra statistically, so that those resulting from a specific process error are recognized prior to their potentially incorrect (and damaging) diagnosis. To meet this need, we have developed a series of quality-assurance and in-process control procedures to (a) globally evaluate sources of sample variability, (b) identify outlying mass spectra, and (c) develop quality-control release specifications. From these quality-assurance and control (QA/QC) specifications, we identified 32 mass spectra out of the total 248 that showed statistically significant differences from the norm. Hence, 216 of the initial 248 high-resolution mass spectra were determined to be of high quality and were remodeled by pattern-recognition analysis. Again, we obtained four mass spectral feature set patterns that also exhibited 100% sensitivity and specificity in blinded validation tests (68/68 cancer: including 18/18 stage I, and 43/43 healthy). We conclude that (a) the use of high-resolution MS yields superior classification patterns as compared with those obtained with lower resolution instrumentation; (b) although the process error that we discovered did not have a deleterious impact on the present results obtained from proteomic pattern analysis, the major source of spectral variability emanated from mass spectral acquisition, and not bias at the clinical collection site; (c) this variability can be reduced and monitored through the use of QA/QC statistical procedures; (d) multiple and distinct proteomic patterns, comprising low molecular weight biomarkers, detected by high-resolution MS achieve accuracies surpassing individual biomarkers, warranting validation in a large clinical study.

Psychometric evaluation of the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (Fact/GOG-Ntx) questionnaire for patients receiving systemic chemotherapy.

The purpose of this study was to validate the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) questionnaire. The FACT/GOG-Ntx is the FACT-G plus an eleven-item subscale (Ntx subscale) that evaluates symptoms and concerns associated specifically with chemotherapy-induced neuropathy. Two groups of women with ovarian cancer completed the FACT/GOG-Ntx: one group with known neurotoxicities and one group of chemotherapy-naive women newly diagnosed with ovarian cancer. Levels of patient neuropathy, severity of toxicity, and patient quality of life from diagnosis of ovarian cancer to 12 months post-diagnosis were assessed. The Ntx subscale significantly differentiated the two groups at baseline and 3- and 6-month follow-ups, demonstrating significantly fewer problems among chemotherapy-naive patients than among patients with known neuropathy. The FACT/GOG-Ntx is a reliable and valid instrument for assessing the impact of neuropathy on health-related quality of life. The Ntx subscale demonstrated sensitivity to meaningful clinical distinctions and change over time.

The I1-imidazoline receptor in PC12 pheochromocytoma cells activates protein kinases C, extracellular signal-regulated kinase (ERK) and c-jun N-terminal kinase (JNK).

We sought to further elucidate signal transduction pathways for the I1-imidazoline receptor in PC12 cells by testing involvement of protein kinase C (PKC) isoforms (betaII, epsilon, zeta), and the mitogen-activated protein kinases (MAPK) ERK and JNK. Stimulation of I1-imidazoline receptor with moxonidine increased enzymatic activity of the classical betaII isoform in membranes by about 75% and redistributed the atypical isoform into membranes (40% increase in membrane-bound activity), but the novel isoform of PKC was unaffected. Moxonidine and clonidine also increased by greater than two-fold the proportion of ERK-1 and ERK-2 in the phosphorylated active form. In addition, JNK enzymatic activity was increased by exposure to moxonidine. Activation of ERK and JNK followed similar time courses with peaks at 90 min. The action of moxonidine on ERK activation was blocked by the I1-receptor antagonist efaroxan and by D609, an inhibitor of phosphatidylcholine-selective phospholipase C (PC-PLC), previously implicated as the initial event in I1-receptor signaling. Inhibition or depletion of PKC blocked activation of ERK by moxonidine. Two-day treatment of PC12 cells with the I1/alpha2-agonist clonidine increased cell number by up to 50% in a dose related manner. These data suggest that ERK and JNK, along with PKC, are signaling components of the I1-receptor pathway, and that this receptor may play a role in cell growth.

Evaluating the total costs of chemotherapy-induced toxicity: results from a pilot study with ovarian cancer patients.

PURPOSE: While chemotherapy-related toxicities affect cancer patients' activities of daily living and result in large expenditures of medical care for treatment, few studies have assessed the out-of-pocket and indirect costs incurred by patients who experience toxicity. The objective of this study was to evaluate the feasibility of obtaining detailed and comprehensive cost information from patients who experienced neutropenia, thrombocytopenia, or neurotoxicity during treatment. METHODS: Ovarian cancer patients who experienced chemotherapy-associated hematologic or neurologic toxicities were asked to record detailed information about hospitalization, laboratories, physician visits, phone calls, home visits, medication, medical devices, lost productivity, and caregivers. Resource estimates were converted into cost units, with direct medical cost estimates based on hospital cost-accounting data and indirect costs (i.e., productivity loss) on modified labor force, employment, and earnings data. RESULTS: Direct medical costs were highest for neutropenia (mean of $7,546/episode), intermediate for thrombocytopenia (mean of $3,268/episode), and lowest for neurotoxicity (mean of $688/episode). Indirect costs relating to patient and caregiver work loss and payments for caregiver support were substantial, accounting for $4,220, $3,834, and $4,282 for patients who developed neurotoxicity, neutropenia, and thrombocytopenia, respectively. The total costs of chemotherapy-related neurotoxicity, neutropenia, and thrombocytopenia were $4,908, $11,830, and $7,550. CONCLUSION: Our study has shown that, with the assistance of patients who are experiencing toxicity, estimation of the total costs of cancer-related toxicities is feasible. Indirect costs, while not included in prior estimates of the costs of toxicity studies, accounted for 34% to 86% of the total costs of cancer supportive care.