Using PET-CT in the restaging of primitive mediastinal B-cell lymphoma (PMBCL) after chemotherapy: which criteria should we use?

AIM: Primitive mediastinal B-cell lymphoma (PMBCL) is a relatively rare form of non-Hodgkin lymphoma (NHL), typically concerning the youngster, with an aggressive course and poor prognosis. The therapy generally consists of high dose chemotherapy followed by radiotherapy. PET-CT is used at staging, restaging after chemotherapy and after radiotherapy, or when relapse is suspected. Aim of the study was to compare different criteria in the evaluation of response to chemotherapy in this setting. METHODS: Thirty-eight patients with PMBCL (15 M, 23 F, median age 33 yrs [range 18-79]), all treated with chemo-immunotherapy and radiotherapy, who had undergone baseline (b-PET) and end of chemotherapy (f-CHT-PET) 18F-FDG-PET-CT scans at our institution between July 2004 and September 2014 were retrospectively re-evaluated; the median follow-up was 42 months (range 4-109), at which 4/38 (11%) had died, 5/38 (13%) were in partial response (PR) and 29/38 (76%) were in complete response (CR). The primary endpoint was progression-free survival (PFS), while the secondary one was overall survival (OS), according to the Cheson criteria. SUV max of the mediastinal disease mass at staging, of the residual mass at CT after chemo-immunotherapy, SUV max of the liver and of the mediastinal blood pool (MBP) were calculated for all patients. RESULTS: In our population, we observed that: 1) visual criteria performs better when positivity-negativity threshold is set at point 3 of the 5-point scale (5-PS); 2) semiquantitative approach by use of Δ SUV max performs better when the threshold is set at 66% decrease: in fact, at Δ SUV max analysis with 66% decrease, 9 patients resulted positive at the test (Δ SUV max ≤66%), 29 negative (Δ SUV max >66%). CONCLUSION: In our population Δ SUV max could be working well in these patients because the baseline values are very high and very homogeneous. Our data, though limited in numerosity of patients and events, suggests that in this particular setting the use of the 5-PS reporting system could not be the best tool available; on the other hand, Δ SUV max could prove to be reliable in the evaluation of response to chemotherapy.

Transcontinental anaesthesia: a pilot study.

BACKGROUND: Although telemedicine is one of the key initiatives of the World Health Organization, no study has explored the feasibility and efficacy of teleanaesthesia. This bi-centre pilot study investigates the feasibility of transcontinental anaesthesia. METHODS: Twenty patients aged ≥ 18 yr undergoing elective thyroid surgery for ≥ 30 min were enrolled in this study. The remote and local set-up was composed of a master-computer (Montreal) and a slave-computer (Pisa). Standard Internet connection, remote desktop control, and video conference software were used. All patients received total i.v. anaesthesia controlled remotely (Montreal). The main outcomes were feasibility, clinical performance, and controller performance of transcontinental anaesthesia. The clinical performance of hypnosis control was the efficacy to maintain bispectral index (BIS) at 45: 'excellent', 'good', 'poor', and 'inadequate' control represented BIS values within 10, from 11 to 20, from 21 to 30, or >30% from target. The clinical performance of analgesia was the efficacy to maintain Analgoscore values at 0 (-9 to 9); -3 to +3 representing 'excellent' pain control, -3 to -6 and +3 to +6 representing 'good' pain control, and -6 to -9 and +6 to +9 representing 'insufficient' pain control. The controller performance was evaluated using Varvel parameters. RESULTS: Transcontinental anaesthesia was successful in all 20 consecutive patients. The clinical performance of hypnosis showed an 'excellent and good' control for 69% of maintenance time, and the controller performance showed an average global performance index of 57. The clinical performance of analgesia was 'excellent and good' for 92% of maintenance time, and the controller performance showed a global performance index of 1118. CONCLUSIONS: Transcontinental anaesthesia is feasible; control of anaesthesia shows good performance indexes. Clinical registration number NCT01331096.

Reversal of profound and "deep" residual rocuronium-induced neuromuscular blockade by sugammadex: a neurophysiological study.

BACKGROUND: Sugammadex is the first of a new class of selective relaxant binding drugs developed for the rapid and complete reversal of neuromuscular blockade (NMB) induced by the aminosteroid neuromuscular blocking drugs rocuronium and vecuronium. Neuromuscular blocking drugs block the transmission from the peripheral nerve to the muscle units, with reduction and disappearance of the evoked electromyographic activity. Usually, neuromuscular monitoring for the investigational reversal drug is performed by calibrated acceleromyography. The efficacy of sugammadex in reversing profound and "deep" residual rocuronium-induced NMB using myogenic motor evoked potentials (mMEPs) monitoring was evaluated. METHODS: In this prospective trial, 30 consenting patients undergoing propofol-remifentanil anesthesia for spine surgery were enrolled and divided into two groups: Group 1, reversal of profound NMB (sugammadex 16 mg/Kg, 3 minutes after rocuronium 1.2 mg/Kg) and Group 2, reversal of "deep" residual NMB (sugammadex 4 mg/Kg, 15 minutes after rocuronium 0.6 mg/Kg). Myogenic MEPs registrations of upper and lower limbs and the diaphragm were performed, as well as TOF monitoring. RESULTS: After injection of 4 mg/Kg of sugammadex, the means of recovery time of the basal mMEPs amplitudes (diaphragm, and lower limbs and upper limbs) were 124±9.6, 143±163, 151±207 sec, respectively whereas after 16 mg/Kg of sugammadex the times were 109±13.8, 124±0.6, and 135±14.1 sec. Times to TOF ratio 0.9 were 114±75 and 186±105 sec in Group 1 and 2, respectively. No serious adverse effects related to sugammadex and to electrical stimulation were reported. No reoccurrence of neuromuscular block was observed. CONCLUSION: Neurophysiological monitoring using mMEPs confirmed that sugammadex provided a complete recovery from profound and "deep" residual rocuronium-induced neuromuscular blockade.

Xenon exposure in the neonatal rat brain: effects on genes that regulate apoptosis.

BACKGROUND: In the developing rodent brain, exposure to volatile anesthetics causes widespread neuronal apoptosis in several regions of the brain. Increasing evidence points to a possible neuroprotective role for the anesthetic gas xenon, following neuronal injury. To address this gap in understanding, we explored the transcriptional consequences of xenon in the brains of postnatal day 7 (P7) rats exposed to xenon compared to those of air-breathing animals, with particular emphasis on the mRNA transcript levels of Akt and c-Jun N-terminal kinase kinase 1 (JNKK1), which are important for cell survival and the activation of extrinsic neuroapoptotic pathways, respectively. METHODS: P7 Sprague/Dawley rats were exposed to air (75% nitrogen, 25% oxygen) or xenon (75% xenon, 25% oxygen) for 120 min (N=6/group). Forebrains were harvested for reverse transcription polymerase chain reaction, which enabled quantification of Akt and JNKK1 mRNA transcripts. Suppression subtractive hybridization was used to explore the "genetic signature" of xenon exposure. RESULTS: Compared to control air-breathing animals, xenon-breathing rats exhibited a 0.7-fold decrease in Akt mRNA expression (P<0.01) and a 1.6-fold increase in JNKK1 mRNA levels (P<0.05). CONCLUSION: The concomitant decrease in the Akt mRNA expression level and increase in the JNKK1 mRNA transcript level provide evidence that xenon has a neuroapoptotic effect in the developing rodent forebrain. Given these results, further study into the paradoxical neuroprotective and neuroapoptotic effects of xenon is warranted.

Prospective multicenter study on epidemiology of acute kidney injury in the ICU: a critical care nephrology Italian collaborative effort (NEFROINT).

Acute kidney injury (AKI) is an independent risk factor for mortality in critically ill patients whose epidemiology has been made unclear in the past by the use of different definitions across various studies. The RIFLE consensus definition has provided a unifying definition for AKI leading to large retrospective studies in different countries. The present study is a prospective observational multicenter study designed to prospectively evaluate all incident admissions in 10 Intensive Care Units (ICUs) in Italy and the relevant epidemiology of AKI. A simple user-friendly web-based data collection tool was created with the scope to serve for this study and to facilitate future multicenter collaborative efforts. We enrolled 601 consecutive patients into the study; 25 patients with End-Stage Renal Disease were excluded leaving 576 patients for analysis. The median age was 66 (IQR 53-76) years, 59.4% were male, while median SAPS II and APACHE II scores were 43 (IQR 35-54) and 18 (IQR 13-24), respectively. The most common diagnostic categories for ICU admission were: respiratory (27.4%), followed by neurologic (17%), trauma (14.4%), and cardiovascular (12.1%). Crude ICU and hospital mortality were 21.7% and median ICU length of stay was 5 days (IQR 3, 14). Of 576 patients, 246 patients (42.7%) had AKI within 24 hours of ICU admission while 133 developed new AKI later during their ICU stay. RIFLE-initial class was Risk in 205 patients (54.1%), Injury in 99 (26.1%) and Failure in 75 (19.8%). Progression of AKI to a worse RIFLE class was seen in 114 patients (30.8% of AKI patients). AKI patients were older, with higher frequency of common risk factors. 116 AKI patients (30.6%) fulfilled criteria for sepsis during their ICU stay, compared to 33 (16.7%) of non-AKI patients (P<0.001). 48 patients (8.3%) were treated with renal replacement therapy (RRT) in the ICU. Patients were started on RRT a median of 2 (IQR 0-6) days after ICU admission. Among AKI patients, they were started on RRT a median of 1 (IQR 0-4) days after fulfilling criteria for AKI. Median duration of RRT was 5 (IQR 2-10) day. AKI patients had a higher crude ICU mortality (28.8% vs. non-AKI 8.1%, P<0.001) and longer ICU length of stay (median 7 days vs. 3 days [non-AKI], P<0.001). Crude ICU mortality and ICU length of stay increased with greater severity of AKI. Two hundred twenty five patients (59.4% of AKI patients) had complete recovery of renal function, with a SCr at time of ICU discharge which was ≤120% of baseline; an additional 51 AKI patients (13.5%) had partial renal recovery, while 103 (27.2%) had not recovered renal function at the time of death or ICU discharge. Septic patients had more severe AKI, and were more likely to receive RRT with less frequency of renal function recovery. Patients with sepsis had higher ICU mortality and longer ICU stay. The study confirms previous analyses describing RIFLE as an optimal classification system to stage AKI severity. AKI is indeed a deadly complication for ICU patients where the level of severity correlated with mortality and length of stay. The tool developed for data collection resulted user friendly and easy to implement. Some of its features including a RIFLE class alert system, may help the treating physician to collect systematically AKI data in the ICU and possibly may guide specific decision on the institution of renal replacement therapy.

Nitrous oxide discretely up-regulates nNOS and p53 in neonatal rat brain.

AIM: Animal studies suggest that neuronal cell death often results from anesthetic administration during synaptogenesis. Volatile anesthetics are strongly involved in triggering neuronal apoptosis, whereas other inhalational agents (xenon) demonstrate protective effects. Nitrous oxide (N2O) has modest pro-apoptotic effects on its own and potent, synergistic toxic effects when combined with volatile agents. Recent findings suggest that, during periods of rapid brain development, the enhanced neurodegeneration triggered by anesthetic drugs may be caused by a compensatory increase in intracellular free calcium, a potent activator of neuronal nitric oxide synthase (nNOS). Anesthesia-induced neuro-apoptosis is also activated via the intrinsic and the extrinsic apoptotic pathways because both pathways involve p53, a key regulatory gene. The molecular events related to neuronal cell apoptosis are not completely understood. To gain further insight into the events underlying neuro-apoptosis, we analyzed the transcriptional consequences of N2O exposure on nNOS, iNOS and p53 mRNA levels. METHODS: The study used 2 groups of postnatal day seven Sprague/Dawley rats (N=6 each) that were exposed for 120 minutes to air (75% N2, 25% O2) or N2O (75% N2O, 25% O2; this N2O concentration is commonly used to induce anesthesia and has been demonstrated to trigger neurodegeneration in postnatal day seven rats). Total RNA was isolated from each brain and expression analyses on iNOS and nNOS transcripts were performed using relative Real-Time C-reactive protein PCR (using G3PDH as a housekeeping gene). A semi-quantitative RT-PCR analysis was performed on the p53 transcript (using Ciclophylin A as a housekeeping gene). RESULTS: Statistical analysis (REST 2005) revealed a significant, 11-fold up-regulation (P=0.026) of the nNOS transcript but no significant changes in iNOS transcription. The p53 mRNA was up-regulated almost 2-fold (P=0.0002; Student's t-Test; GraphPad Prism 4.00) in N2O-treated samples relative to room-air samples. CONCLUSION: Our preliminary data show that N2O induced a selective increase in nNOS and p53 transcription. These new findings provide evidence of pro-apoptotic action by N2O and may shed new insight on its toxic effects; however, further investigations are necessary.

Xenon preconditioning confers neuroprotection regardless of gender in a mouse model of transient middle cerebral artery occlusion.

Xenon preconditioning induces tolerance to the consequences of an injurious stimulus such as cerebral ischaemia. There have been surprisingly few studies investigating gender difference in the efficacy of pharmacological preconditioning, despite the known ability of oestradiol to exert neuroprotectant activity. We explored this paradigm using a mouse model of transient middle cerebral artery occlusion. C57BL/6 mice both male and female received either 2 h of 70% xenon (preconditioning) or 70% nitrogen (control) balanced with oxygen. Twenty-four hours later animals underwent 1 h of middle cerebral artery occlusion and then allowed to recover. After a further 24 h, functional neurological outcome and cerebral infarct size were evaluated. Western blotting was used to detect activity of signalling pathways involving hypoxia-inducible factor (HIF)-1alpha and phospho-Akt for the preconditioning effect. Both xenon preconditioned male and females showed improved functional outcome on focal deficit scales (P<0.05). Cerebral infarct volumes were significantly reduced in both xenon treated male and females (P<0.01). There was no significant difference between the male and female cohorts. HIF-1alpha and phospho-Akt were quantitatively upregulated in both sexes. Our data suggested that xenon preconditioning improved histological and neurological functional outcome in both gender in a stroke model of mice.

A fatal case of airway obstruction by an organic one-way valve.

We report a fatal case of airway obstruction. A tracheostomized, spontaneously breathing 39-year-old man developed dyspnea, cardiac, and respiratory arrest after tracheal cannula replacement. Inspection of the cannula showed a blood clot obstructing the tube. Autopsy showed pink foam in the trachea, pulmonary hyperinflation, and congested lung parenchyma. Histological examination showed acute pulmonary emphysema without any sign of blood inhalation. The probable pathophysiological mechanism is a clot creating a one-way valve allowing inspiration but not expiration, resulting in dyspnea and pulmonary hyperinflation.

Feasibility of the sentinel node biopsy in anal cancer.

AIM: Anal cancer is a rare neoplasm. According to a European Organization for Research and Treatment of Cancer multivariate analysis, synchronous inguinal lymph node metastasis occurs in 10-25% of patients and constitutes an independent prognostic factor for local failure and overall mortality. METHODS: Inguinal lymph node status was assessed using the sentinel node technique in 35 patients with anal cancer. RESULTS: Histology revealed 23 squamous carcinomas, 10 basaloid carcinomas, 1 squamous carcinoma with basaloid areas and 1 spinocellular epithelioma associated with areas of Bowen's disease. Disease stage was T1 in 5 patients, T2 in 18, T3 in 11 and T4 in 1 patient. Lympho-scintigraphy using a GE Millennium gamma camera was performed after peritumoral injection of 37 MBq of 99mTc colloid. Surgical sentinel node biopsy with a portable Scintiprobe MR 100 (Politech, Carsoli, Italy) had a detection rate of 97.1%. Inguinal metastases were detected in 7 (20%) patients, in 2 of which metastasis was bilateral. CONCLUSIONS: Given the correlation between prognosis and node involvement, sentinel node biopsy can be considered a simple method for adequate pretreatment staging of anal carcinoma. Use of the technique could avert the need for prophylactic inguinal radiotherapy in N0-N1 patients, thus reducing the morbidity associated with inguinal radiotherapy. Consistent follow-up is required to evaluate long-term results:

Reversal of rocuronium-induced neuromuscular block with sugammadex is faster than reversal of cisatracurium-induced block with neostigmine.

BACKGROUND: Reversal of the residual effect of rocuronium or cisatracurium by neostigmine may be slow and associated with side-effects. This randomized, safety-assessor-blinded study compared the efficacy of sugammadex, a selective relaxant binding agent for reversal of rocuronium-induced neuromuscular block, with that of neostigmine for reversal of cisatracurium-induced neuromuscular block. The safety of sugammadex and neostigmine was also evaluated. METHODS: Adult surgical patients (ASA class I-III) were randomized to sugammadex 2.0 mg kg(-1) for reversal of block induced by rocuronium 0.6 mg kg(-1), or neostigmine 50 microg kg(-1) for reversal of block induced by cisatracurium 0.15 mg kg(-1). Anaesthesia was induced and maintained using i.v. propofol and remifentanil, fentanyl, or sufentanil. Neuromuscular function was monitored using acceleromyography (TOF-Watch SX). Sugammadex or neostigmine was administered at reappearance of T(2). The primary efficacy variable was time for recovery of the train-of-four (TOF) ratio to 0.9. RESULTS: Eighty-four patients were randomized, 73 of whom received sugammadex (n=34) or neostigmine (n=39). Time from start of administration of reversal agent to recovery of the TOF ratio to 0.9 was 4.7 times faster with sugammadex than with neostigmine (geometric mean=1.9 vs 9.0 min, P<0.0001). Reversal of block was sustained in all patients. There were no serious adverse effects from either reversal agent and no significant changes in any measure of safety, except for similar elevations in urinary N-acetyl glucosaminidase in both groups. CONCLUSIONS: Sugammadex 2.0 mg kg(-1) administered at reappearance of T(2) was significantly faster in reversing rocuronium-induced blockade than neostigmine was in reversing cisatracurium-induced block.

Implicit and explicit memory formation: influence of gender and cultural habits.

The study was aimed to investigate whether impending surgery, considered as a stressful life event, might interfere with memory formation like other stress and anxiety conditions do. Results do not support the hypothesis. Implicit and explicit memory performance are both unaffected by presurgery condition and seem influenced, rather, by subjects gender, education and cultural habits. Females perform generally better than males and, regardless of age and sex, higher educated individuals score higher on the explicit memory task. The habits of reading books and doing crosswords are associated to best performance on explicit and implicit memory task respectively.

Risk factors assessment of the difficult airway: an italian survey of 1956 patients.

Over the last decade, there has been a heightened awareness and an increase in the amount of literature being published on recognition and prediction of the difficult airway. During the preoperative evaluation of the airway, a thorough history and physical specifically related to the airway should be performed. Various measurements of anatomic features and noninvasive clinical tests can be performed to enhance this assessment. In this study we correlated the Mallampati modified score and several other indexes with the laryngoscopic view to identify anatomical and clinical risk factors related to the difficult airway. We prospectively collected data on 1956 consecutive patients scheduled to receive general anesthesia requiring endotracheal intubation for elective surgery. The Mallampati classification versus the Cormack-Lehane (C-L) linear correlation index was 0.904. A Mallampati Class 3 correlated with a C-L Grade 2 (0.94), whereas a Mallampati Class 4 correlated with a C-L Grade 3 (0.85) and a C-L Grade 4 (0.80). Operator evaluation, performed by a simplified tracheal intubation difficulty scale, showed a linear correlation of 0.96 compared with the C-L groups. Although there is a correlation between oropharyngeal volume and difficult intubation, the Mallampati score by itself is insufficient for predicting difficult endotracheal intubation.

Anesthesia in Italy in 2000: sciences and working practice.

BACKGROUND: To survey current anaesthesiology practice in Italy. METHODS: We submitted to 1260 Italian anaesthesiologists in 12 different regional places a structured form aimed at surveying their common work practice. Our sample consisted of anaesthesiologists, age 26-63, with 1-35 years of professional practice. We believe that our sample represents about 7-10% of Italian anaesthesiologists, reflecting a global number of 600,000 procedures performed during 2000. The results have been analyzed by an Excel spreadsheet and they are reported as mean of the percentage of use declared in the case of drugs, and as percentage of the responses in the case of procedure and monitoring systems used. Furthermore we divided our sample population according to two criteria: principal place of work (general operating rooms (OR), subspecialty ORs, ICU) and years of anaesthesiology practice (<5>). The results have been crossmatched within and between the subgroups. RESULTS: The survey showed a composite state of anaesthesia practice in Italy. The main differences are between the youngest and the oldest anaesthesiologists and between the anaesthesiologists working mainly in the ICU and in the ORs. CONCLUSIONS: Italian anaesthesia practice is still a very composite reality.

Effects of repeated exposures to xenon on rat adrenal cortex ultrastructure.

Xenon has many properties of the ideal anaesthetic and it has been proposed to replace classic volatile anaesthetics. Although some studies demonstrated that xenon does not induce gross morphological changes in major organs, little is known on its possible ultrastructural effects. The present study investigates the subcellular effects of repeated exposures to 70% xenon on rat adrenal cortex in comparison with N2O. Animals were divided into four groups: xenon-exposed, N2O-exposed, sham-exposed and controls. Exposed rats were placed into a sealed cage to breathe the respective gas mixture for 2.5 h/day for a week. Specimens of adrenal cortex for electron microscopy and blood samples for determination of corticosterone plasma levels were taken at the end of the last exposure or one week after the last exposure (recovery). Adrenal cortex from N2O- and sham-exposed rats mainly showed dilation of endoplasmic reticulum, whereas xenon-exposed rats also exhibited several cells with lipid droplets appearing subdivided into smaller droplets, irregular in shape and size. In all experimental groups, corticosterone plasma levels increased in comparison to controls. Both ultrastructural and hormonal changes were not detected anymore after one week from the last exposure. These findings indicate that xenon is able to induce subcellular changes in rat adrenal cortex, mainly at the level of lipid structures. The transient changes induced by xenon suggest that this gas can be regarded as a safer anaesthetic.