Impact of the type of imaging modality on target volumes delineation and dose distribution in pharyngo-laryngeal squamous cell carcinoma: comparison between pre- and per-treatment studies.

BACKGROUND AND PURPOSE: It has been shown that the use of pre-treatment FDG-PET impacted on the GTV delineation of pharyngo-laryngeal tumors. The goals of this study were to evaluate (1) the impact of FDG-PET GTV on dose distribution, and (2) the impact of per-treatment re-imaging on target volume delineation and dose distribution. MATERIALS AND METHODS: Eighteen patients with squamous cell carcinoma of the oropharynx or larynx/hypopharynx were treated with curative intent by forward planning IMRT. Prior to treatment and on average after a dose of 46 Gy, all patients underwent contrast-enhanced CT, MRI and FDG-PET. After coregistration, GTVs were delineated manually on CT and MRI and automatically on FDG-PET. From these volumes, CTVs and PTVs were derived using consistent guidelines. Planning was performed using conformal radiotherapy. RESULTS: GTVs, CTVs and PTVs based on pre-treatment FDG-PET were significantly smaller than those based on pre-treatment CT. Such difference in target volumes (TV) translated into a significant reduction in the irradiated volumes (reduction of 13 and 18% of the V50 and V95, respectively), Dmean to ipsilateral parotids (30.7 and 38.6% for FDG-PET and CT based plans, respectively) and to controlateral parotids (11.2 and 14.4% for FDG-PET and CT based plans, respectively). TVs based on per-treatment CT or MRI were also significantly smaller compared to those delineated from pre-treatment CT. Volumes delineated with MRI were significantly smaller than those delineated with CT. Due to radiotherapy-induced peri-tumoral inflammation, automatic delineation of FDG-PET GTV could not be performed. Such reductions in TVs translated into a reduction of the irradiated volumes compared to pre-treatment CT planning (reduction for V50 of 19 and 32%, and for V95 of 22 and 40%, for CT and MRI, respectively); Dmean to the ipsilateral parotids were also reduced (ipsilateral parotid Dmean of 20.4% for CT and of 20.1% for MRI compared to 24.7% for pre-treatment CT). CONCLUSIONS: The use of pre-treatment FDG-PET and per-treatment CT or MRI significantly impacts on the delineation of TVs in pharyngo-laryngeal SCC, translating into more normal tissue sparing after conformal radiotherapy planning.     

Deprived areas and attendance to screening of cervix uteri cancer in a French region

Objectives: To examine the relationship between deprivation and attendance to cervical cancer screening. Methods: Three deprivation indices (Carstairs, UnderPrivileged Area, Department of Environment) were calculated for women aged 25–65 attending a 1993–95 cervical cancer screening program (Doubs département, France), with 594 municipalities as statistical units. Weighted multivariate linear regressions were performed, with attendance rate as the dependent variable, and the three deprivation indices in turn as independent variables along with women's mean age, average net income, density of (para)medical amenities, density of population and proportion of women. Results: Per municipality women were numbered 1–29,822 (mean 210). In multivariate models, the three deprivation indices were negatively linked to attendance rate, and so were mean age of women and density of population. Average net income, proportion of women, and density of (para)medical amenities (nurses, laboratories, ambulances, physicians, dentists) were positively associated with attendance rate. Conclusions: In early stages, cervical cancer screening programs should account for populations living in deprived areas, through focused health promotion efforts and easier access to screening facilities.     

Intrarenal teratoma in a newborn child

A case of intrarenal teratoma in a newborn child is reported. The scarcity as well as the clinical and radiological signs of this lesion are emphasized and the difficulties to distinguish it from a nephroblastoma are analyzed. Solid intrarenal tumours in the infant and the newborn child are in nearly all cases nephroblastomas. All other types of solid tumours (benign or malignant) are exceptional. This induces us to report the present case.     

Are inflammatory cytokines the common link between cancer-associated cachexia and depression?

The prevalence of depression among patients diagnosed with cancer is higher than among the general medical population and is associated with faster tumor progression and shortened survival time. Cancer-related depression often occurs in association with anorexia and cachexia, although until recently the relationship between these conditions has not been well understood. Cachexia is associated with poorer quality of life and survival outcomes and is theeventual cause of death in approximately 30% of all patients with cancer. Recent evidence has linked elevated levels of inflammatory cytokines with both depression and cachexia, and experiments have shown that introducing cytokines induces depression and cachectic symptoms in both humans and rodents, suggesting that there may be a common etiology at the molecular level. Therapeutic agents targeting specific cytokine molecules, such as interleukin-6 or tumor necrosis factor-alpha, are currently being evaluated for their potential to simultaneously treat both depression and cachexia pharmacologically. This review summarizes the available data suggesting a dual role for cytokines in the development of cancer-related depression and cachexia and describes how biologic therapies targeting specific cytokines may improve outcomes beyond depression and cachexia, such as survival and quality of life.     

Functional interactions between nucleotide binding domains and leukotriene C4 binding sites of multidrug resistance protein 1 (ABCC1)

Multidrug resistance protein 1 (MRP1) is a member of the "C" branch of the ATP-binding cassette transporter superfamily. The NH(2)-proximal nucleotide-binding domain (NBD1) of MRP1 differs functionally from its COOH-proximal domain (NBD2). NBD1 displays intrinsic high-affinity ATP binding and little ATPase activity. In contrast, ATP binding to NBD2 is strongly dependent on nucleotide binding by NBD1, and NBD2 is more hydrolytically active. We have demonstrated that occupancy of NBD2 by ATP or ADP markedly decreased substrate binding by MRP1. We have further explored the relationship between nucleotide and substrate binding by examining the effects of various ATP analogs and ADP trapping, as well as mutations in conserved functional elements in the NBDs, on the ability of MRP1 to bind the photoactivatable, high-affinity substrate cysteinyl leukotriene C(4) (LTC(4))(.) Overall, the results support a model in which occupancy of both NBD1 and NBD2 by ATP results in the formation of a low-affinity conformation of the protein. However, nonhydrolyzable ATP analogs (beta,gamma-imidoadenosine 5'-triphosphate and adenylylmethylene diphosphonate) failed to substitute for ATP or adenosine 5'-O-(thiotriphosphate) (ATPgammaS) in decreasing LTC(4) photolabeling. Furthermore, mutations of the signature sequence in either NBD that had no apparent effect on azido-ATP binding abrogated the formation of a low-affinity substrate binding state in the presence of ATP or ATPgammaS. We suggest that the effect of these mutations, and possibly the failure of some ATP analogs to decrease LTC(4) binding, may be attributable to an inability to elicit a conformational change in the NBDs that involves interactions between the signature sequence and the gamma-phosphate of the bound nucleotide.     

Three-dimensional rotational angiography: introduction of an adjunctive tool for successful transarterial chemoembolization

Transcatheter arterial embolization (TACE) is a minimally invasive procedure that requires precise visualization of the feeding vessels to liver tumors for proper catheter placement and effective therapy. The use of three-dimensional (3D) rotational angiography (RA) can be extremely useful to the interventional radiologist during TACE while the patient is on the catheterization table. This report demonstrates the role of 3D RA in interventional oncology by presenting two cases of hepatocellular carcinoma with complex vascular anatomy successfully treated because of the information provided by this new technology.     

Transcatheter arterial chemoembolization in unresectable cholangiocarcinoma: initial experience in a single institution

PURPOSE: Unresectable cholangiocarcinoma carries a dismal prognosis, with median survival times ranging from 6 to 12 months from the time of diagnosis. Palliative therapies have been disappointing and have not been shown to significantly prolong survival. Conversely, transcatheter arterial chemoembolization (TACE) has been effective in prolonging the lives of patients with hepatocellular carcinoma but has not been used against cholangiocarcinoma. Therefore, the purpose of the present study was to assess the safety and efficacy (ie, survival) of TACE in patients with unresectable intrahepatic cholangiocarcinoma. MATERIALS AND METHODS: Seventeen patients with unresectable cholangiocarcinoma were treated with one or more cycles of TACE between 1995 and 2004 at our institution. Follow-up imaging was performed on all patients 4-6 weeks after each TACE procedure to determine tumor response and need for further treatment. Survival was calculated with use of the Kaplan-Meier survival curve. RESULTS: The median survival for 17 patients treated with TACE was 23 months. Two patients with previously unresectable disease underwent successful resection after TACE. The procedure was well tolerated by 82% of the patients, who experienced no side effects or mild side effects that quickly resolved with conservative therapy alone. Two patients had minor complications (12%), which were managed successfully, and one had a major complication that resulted in a fatal outcome. This patient had a rapidly declining course from the time of diagnosis and died shortly after TACE. CONCLUSIONS: The results suggest that TACE was effective at prolonging survival of patients with unresectable cholangiocarcinoma. Therefore, for these patients, TACE may be an appropriate palliative therapy.     

Thromboprophylaxis in neurosurgery and head trauma

The incidence of deep vein thrombosis (DVT) is between 20 and 35% using contrast venography, with a rate of symptomatic DVT between 2.3 and 6% in neurosurgery without any prophylaxis. The risk of DVT is poorly evaluated in head injured patients but is around 5%. Specific risk factors in neurosurgery are: a motor deficit, a meningioma or malignant tumour, a large tumour, age over 60 years, surgery lasting more than 4 hours, a chemotherapy. The benefit of mechanical methods or low molecular weight heparin (LMWH) for the prevention of DVP in neurosurgery is demonstrated (grade A). Each method decreases the risk by about 50%. A postoperative prophylaxis with a LMWH does not seem to increase the risk of intracranial bleeding (grade C). There is no demonstrated benefit to begin a prophylaxis with LMWH before the intervention. The duration of the prophylaxis is 7 to 10 days but this has not been scientifically determined.     

Dynamic evolution of coagulopathy in the first day of severe sepsis: relationship with mortality and organ failure

OBJECTIVE: To determine whether changes in coagulation biomarkers during the first day of severe sepsis correlate with progression from single to multiple organ failure and subsequent death. DESIGN: Analysis of secondary endpoints in a prospective, randomized, placebo-controlled, multinational clinical trial (PROWESS). SETTING: The study involved 164 medical centers. PATIENTS: A total of 840 patients who met criteria for severe sepsis and were randomized to receive placebo plus supportive care. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Coagulation biomarkers, prothrombin time, antithrombin activity, and D-dimer and protein C levels were measured, and Sequential Organ Failure Assessment was performed daily. Multiple logistic regression analysis identified baseline antithrombin activity <54% and changes in prothrombin time, D-dimer, and antithrombin activity during the first calendar day after the onset of the first sepsis-induced organ dysfunction (i.e., the first day of severe sepsis, day 1) as predictive of 28-day mortality (p < or = .01). A composite coagulopathy score was determined using points for predetermined levels of change from baseline to day 1. The composite coagulopathy score correlated with progression from single to multiple organ failure (p = .0007), time to resolution of organ failure (p = .0004), and 28-day mortality (p < .0001). Combining the composite coagulopathy score with the Acute Physiology and Chronic Health Evaluation (APACHE) II score improved ability to identify patients who would progress to multiple organ failure (area under receiver operating characteristic curve 0.61 APACHE II vs. 0.65 APACHE II + composite coagulopathy score) and who would die (area under receiver operating characteristic curve 0.69 APACHE II vs. 0.74 APACHE II + composite coagulopathy score). CONCLUSIONS: Continuation or worsening of coagulopathy during the first day of severe sepsis was associated with increased development of new organ failure and 28-day mortality. These results further suggest that coagulation abnormalities contribute to organ failure and death.