Procedural (Conscious) Sedation and Analgesia in Emergency Setting: How to Choose Agents?

Pain has long been defined as an unpleasant sensory and emotional experience originating from any region of the body in the presence or absence of tissue injury. Physicians involved in acute medicine commonly undertake a variety of invasive and painful procedures that prompt procedural sedation and analgesia (PSA), which is a condition sparing the protective airway reflexes while depressing the patient's awareness of external stimuli. This state is achieved following obtaining the patient's informed consent, necessary point-ofcare monitoring, and complete recording of the procedures. The most commonly employed combination for PSA mostly comprises short-acting benzodiazepine (midazolam) and a potent opioid, such as fentanyl. The biggest advantage of opioids is that despite all the powerful effects, upper airway reflexes are preserved and often do not require intervention. Choices of analgesic and sedative agents should be strictly individualized and determined for the specific condition. The objective of this review article was to underline the characteristics, effectiveness, adverse effects, and pitfalls of the relevant drugs employed in adults to facilitate PSA in emergency procedures.

Diagnostic and Prognostic Roles of Procalcitonin and Other Tools in Community-Acquired Pneumonia: A Narrative Review.

Community-acquired pneumonia (CAP) is among the most common causes of death and one of the leading healthcare concerns worldwide. It can evolve into sepsis and septic shock, which have a high mortality rate, especially in critical patients and comorbidities. The definitions of sepsis were revised in the last decade as "life-threatening organ dysfunction caused by a dysregulated host response to infection". Procalcitonin (PCT), C-reactive protein (CRP), and complete blood count, including white blood cells, are among the most commonly analyzed sepsis-specific biomarkers also used in pneumonia in a broad range of studies. It appears to be a reliable diagnostic tool to expedite care of these patients with severe infections in the acute setting. PCT was found to be superior to most other acute phase reactants and indicators, including CRP as a predictor of pneumonia, bacteremia, sepsis, and poor outcome, although conflicting results exist. In addition, PCT use is beneficial to judge timing for the cessation of antibiotic treatment in most severe infectious states. The clinicians should be aware of strengths and weaknesses of known and potential biomarkers in expedient recognition and management of severe infections. This manuscript is intended to present an overview of the definitions, complications, and outcomes of CAP and sepsis in adults, with special regard to PCT and other important markers.

The essential role of radiotherapy in the treatment of Merkel cell carcinoma: a study from the Rare Cancer Network.

PURPOSE: To evaluate the role of postoperative radiotherapy (RT) in Merkel cell carcinoma (MCC). METHODS AND MATERIALS: A retrospective multicenter study was performed in 180 patients with MCC treated between February 1988 and September 2009. Patients who had had surgery alone were compared with patients who received surgery and postoperative RT or radical RT. Local relapse-free survival (LRFS), regional relapse-free survival (RRFS), and distant metastasis-free survival (DMFS) rates were assessed together with disease-free survival (DFS), cancer-specific survival (CSS), and overall survival (OS) rates. RESULTS: Seventy-nine patients were male and 101 patients were female, and the median age was 73 years old (range, 38-93 years). The majority of patients had localized disease (n = 146), and the remaining patients had regional lymph node metastasis (n = 34). Forty-nine patients underwent surgery for the primary tumor without postoperative RT to the primary site; the other 131 patients received surgery for the primary tumor, followed by postoperative RT (n = 118) or a biopsy of the primary tumor followed by radical RT (n = 13). Median follow-up was 5 years (range, 0.2-16.5 years). Patients in the RT group had improved LRFS (93% vs. 64%; p < 0.001), RRFS (76% vs. 27%; p < 0.001), DMFS (70% vs. 42%; p = 0.01), DFS (59% vs. 4%; p < 0.001), and CSS (65% vs. 49%; p = 0.03) rates compared to patients who underwent surgery for the primary tumor alone; LRFS, RRFS, DMFS, and DFS rates remained significant with multivariable Cox regression analysis. However OS was not significantly improved by postoperative RT (56% vs. 46%; p = 0.2). CONCLUSIONS: After multivariable analysis, postoperative RT was associated with improved outcome and seems to be an important component in the multimodality treatment of MCC.

Incidental detection of synchronous primary tumours during staging workup for prostate cancer.

QUESTIONS UNDER STUDY: To assess the prevalence of incidental synchronous primary cancers discovered by abdominal CT scan among prostate cancer patients. METHODS: Patients with prostate cancer in Geneva, Switzerland, were retrospectively analysed regarding incidental diagnosis of synchronous second primary malignancies, including a cohort of 398 patients treated from 1991 through 2001 with radical radiotherapy (RT) and a second cohort of 419 patients treated from 1991 through 2001 by radical prostatectomy (RP) in order to analyse the differences between RT and RP patients. Both cohorts were evaluated regarding incidence of synchronous second primary cancers, compared with that expected in the general population (Standardized Incidence Ratio, SIR). The influence of staging workup on the diagnosis of incidental primary malignancies was studied. RESULTS: Six synchronous cancers (4 renal, 1 pancreatic, 1 rectal) were observed on abdomino-pelvic CT-scan among 480 patients (398 RT patients and 82 RP patients) (1.2%), who had been subjected to staging workup. For renal-cell carcinomas (RCC) in 398 RT patients (RCC) SIR was 18.19 (CI [Confidence Interval] 4.96-46.57), (p <0.001). After exclusion of 12 patients from RP cohort (n:419) in whom the prostate cancer was an incidental finding during surgery for bladder cancer (SIR 33.50 [CI 17.83-57.28]), (p <0.001), 407 patients were observed. There was no synchronous RCC among 325 RP patients who had no CT-scan. CONCLUSIONS: In patients with prostate cancer, abdominopelvic CT staging detects incidental second primary cancers (mostly commonly RCC) with a greater frequency than that expected.

Hypofractionated boost with high-dose-rate brachytherapy and open magnetic resonance imaging-guided implants for locally aggressive prostate cancer: a sequential dose-escalation pilot study.

PURPOSE: To evaluate the feasibility, tolerance, and preliminary outcome of an open MRI-guided prostate partial-volume high-dose-rate brachytherapy (HDR-BT) schedule in a group of selected patients with nonmetastatic, locally aggressive prostatic tumors. METHODS AND MATERIALS: After conventional fractionated three-dimensional conformal external radiotherapy to 64-64.4 Gy, 77 patients with nonmetastatic, locally aggressive (e.g., perineural invasion and/or Gleason score 8-10) prostate cancer were treated from June 2000 to August 2004, with HDR-BT using temporary open MRI-guided (192)Ir implants, to escalate the dose in the boost region. Nineteen, 21, and 37 patients were sequentially treated with 2 fractions of 6 Gy, 7 Gy, and 8 Gy each, respectively. Neoadjuvant androgen deprivation was given to 62 patients for 6-24 months. Acute and late toxicity were scored according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer scoring system. RESULTS: All 77 patients completed treatment as planned. Only 2 patients presented with Grade > or =3 acute urinary toxicity. The 3-year probability of Grade > or =2 late urinary and low gastrointestinal toxicity-free survival was 91.4% +/- 3.4% and 94.4% +/- 2.7%, respectively. Rates of 3-year biochemical disease-free survival (bDFS) and disease-specific survival were 87.1% +/- 4.1% and 100%, respectively. CONCLUSIONS: Boosting a partial volume of the prostate with hypofractionated HDR-BT for aggressive prostate cancer was feasible and showed limited long-term toxicity, which compared favorably with other dose-escalation methods in the literature. Preliminary bDFS was encouraging if one considers the negatively selected population of high-risk patients in this study.

Influence of rectal volume changes during radiotherapy for prostate cancer: a predictive model for mild-to-moderate late rectal toxicity.

PURPOSE: To assess the rectal volume changes during radiotherapy for prostate cancer, to estimate an average rectal dose distribution profile during treatment, and to correlate these parameters with mild-to-moderate late rectal toxicity. MATERIALS AND METHODS: Nine patients with localized prostate cancer underwent virtual CT simulation using a six-field conformal 18-MV photon technique. During treatment, patients underwent weekly pelvic CT scans under simulation conditions. Dosimetries were run with each CT data set using the same beam parameters as in the initial treatment plan. The influence of weekly rectal volume changes on the dose-volume histogram (DVH) profiles was studied. A polynomial function correlating the initial rectal volume with the mean percentage of change in the rectal volume during treatment was used to define a correction factor for rectal DVHs. The model was validated using data from 100 patients treated with 74 Gy according to the same technique. Areas under the curve of the initial rectal DVHs were correlated with toxicity (Radiation Therapy Oncology Group Grade 0 vs. 1-2, Student's t test), with or without the use of the above correction factor. RESULTS: A trend for enlargement of the rectal volume during treatment was observed for most patients in the study with small rectal volumes (<75 cm(3)) at simulation, resulting in an increase in the integral rectal dose by a factor ranging from 1.3 to 2.1. Corrected, but not uncorrected, rectal DVH profiles were strongly predictive of Grade 0 vs. 1-2 late rectal morbidity. CONCLUSIONS: Correcting the area under the curve of the rectal DVH at simulation by a factor that takes into account the projected volume changes during treatment correlates significantly with the probability of mild-to-moderate late rectal toxicity (Grade 1-2). This reliable predictor for mild-to-moderate late rectal morbidity may also be a practical tool for treatment planning.

Dosimetric implications of changes in patient repositioning and organ motion in conformal radiotherapy for prostate cancer.

PURPOSE: To assess the influence of patient repositioning and organ motion on dose distribution within the prostate and the seminal vesicles (clinical target volume, (CTV)). MATERIAL AND METHODS: Nine patients were simulated and treated in the supine position, with an empty bladder, and without immobilization devices. While on treatment, patients underwent weekly pelvic computed tomography (CT) scans under conditions identical to those at simulation. Patients were aligned using lasers on anterior and lateral skin tattoos, onto which lead markers were placed. After each CT scan (n=53) the CTV was redefined by contouring, and a new isocenter was obtained. A six-field technique was used. The field margins around the CTV were 20 mm in the cranio-caudal axis, and 13 mm in the other axes, except in the lateral fields where a 10 mm posterior margin was used. Dose-volume histograms (DVHs) for each organ were compared with those determined at simulation, using the notion of the proportional change in the area under the CTV-DVH curve resulting from a change in treatment plan (cDVH). RESULTS: The reproducibility of the dose distribution was good for the prostate (%cDVH, mean+/-SD: -0.97+/-2.11%) and less than optimal for the seminal vesicles (%cDVH, mean+/-SD: -4.66+/-10.45%). When correlating prostate %cDVH variations with displacements of the isocenter in the Y axis (antero-posterior) the %cDVH exceeded (-)5% in only two dosimetries, both with an isocenter shift of >10 mm. For the seminal vesicles, however, ten out of 53 dosimetries showed a %cDVH exceeding (-) 5%. In nine of these ten dose distribution studies the posterior shift of the isocenter exceeded 8 mm. CONCLUSIONS: Precise targeting of prostate radiotherapy is primarily dependent on careful daily set-up and on random changes in rectal geometry. Margins no less than 10 mm around the prostate and at least 15 mm around the seminal vesicles are probably necessary to insure adequate target coverage with a six-field technique.