Hepatectomy for resectable colorectal cancer metastases--indicators of prognosis, definition of resectability, techniques and outcomes

The field of surgery for liver metastases is evolving rapidly. The proportion of patients viewed as amenable to resection is increasing with surgeons becoming more aggressive and systemic therapy more effective. Surgical resection is associated with low mortality and overall 5-year survival approaching 40%. Best candidates for resection are those with stage I or II colorectal cancer, fewer than 4 hepatic lesions, no lesions larger than 5 cm in diameter, no evidence of extra-hepatic disease, CEA level less than 5 ng/mL, and a disease-free interval of at least 2 years. Perioperative chemotherapy with or without biotherapies, in-situ ablation techniques, portal vein embolization, and staged hepatectomy have extended the indications without lessening the results of liver resection for colorectal metastases.     

Multicenter assessment of ultrasound of the spermatic cord in children with acute scrotum

PURPOSE: Intravaginal or extravaginal spermatic cord torsion is a diagnostic challenge for the surgeon and radiologist. Color Doppler sonography can be inaccurate, leading to dangerous false-negative results. To date, no single reliable test has been able to provide 100% diagnostic accuracy. The direct visualization of the twisted cord during emergency high resolution ultrasonography has been proposed to avoid systematic and abusive surgical exploration. The aim of this multicenter study was to assess the validity and reproducibility of high resolution ultrasonography based management of acute scrotum in children. MATERIALS AND METHODS: A total of 919 patients from 11 European university hospitals underwent color Doppler sonography and high resolution ultrasonography for acute scrotum between 1992 and 2005. The spermatic cord was studied along its complete length to detect a spiral twist. The surgical findings were correlated with the preoperative results. RESULTS: A total of 208 patients had spermatic cord torsion proved at surgery. Intratesticular vascularization was absent in the affected testis in only 158 cases (76%). In contrast, high resolution ultrasonography detected the twist as a snail shell-shaped mass, measuring 7 to 33 mm, in 199 patients (96%). High resolution ultrasonography revealed a linear cord for all other causes of acute scrotum (711 patients) with a specificity of 99%. The radiologist training level was the best predictive factor of high resolution ultrasonography reliability (p <0.05). CONCLUSIONS: High resolution ultrasonography based management of acute scrotum is reliable and reproducible. Thanks to its high sensitivity and specificity for the diagnosis of spermatic cord torsion, high resolution ultrasonography can significantly improve the management of acute scrotum in children.     

Correlation between AV synchrony and device collected AM-VP sequence counter in atrioventricular synchronous leadless pacemakers: A real-world assessment

Introduction

Micra atrioventricular (AV) provides leadless atrioventricular synchronous pacing by sensing atrial contraction (A4 signal). Real-world operation and reliability of AV synchrony (AVS) assessment using device data have not been described. The purposes of this study were to (1) assess the correlation between AVS and atrial mechanical sensed-ventricular pacing (AM-VP) percentages in patients with permanent high-degree AV block and (2) report on the real-world effectiveness of Micra AV.

Methods

The correlation between ECG-determined AVS in-clinic and device-collected %AM-VP was assessed using data from 40 patients with high-degree AV block enrolled in the Micra Atrial tRacking using a Ventricular AccELerometer (MARVEL) 2 study. A retrospective analysis to assess continuously-sampled %AM-VP since last session, device programming, and electrical parameters was performed using Micra AV transmissions from the Medtronic CareLink database. Patients with transmissions ≥180 days postimplant were included.

Results

Among the 40 MARVEL 2 AV block patients with a median %VP of 99.7%, AVS was highly correlated with AM-VP (median AVS 87.1%, median AM-VP 79.1%; R² = 0.764, p < .001). The CareLink cohort included 4384 patients programmed to VDD mode. The mean A4 amplitude was 2.3 ± 1.8 m/s² at implant and 2.3 ± 1.6 m/s² at 28 weeks. In patients with %VP >90% (n = 1662), the median %AM-VP was 74.7%. For the full cohort, median %VP was 65.6% and median projected battery longevity was 10.5 years.

Conclusion

In patients with a high pacing burden, %AM-VP provides a reasonable estimation of AVS. The first large real-world analysis of Micra AV patients with >90% VP showed stable atrial sensing over time with a median %AM-VP, a correlate of AVS, of 74.7%.     

Transcranial magnetic stimulation and other evoked potentials in pediatric multiple sclerosis

In children, multiple sclerosis is rare and has some clinical and paraclinical differences compared with adults. The assessment of corticospinal motor tracts is expected to be relevant because of their frequent early involvement in this disease. Reported are the results of transcranial magnetic stimulation in two children who presented at 12 and 9 years of age with clinically probable and definite multiple sclerosis, respectively. In Patient 1 the excitatory cortical threshold for the upper limbs was abnormally raised. In Patient 2 the latency of the motor-evoked potentials was considerably increased for the right tibialis anterior muscle, with a slowing of the central conduction time. Although these abnormalities may be consistent with central conduction impairment, they may alternatively suggest early axonal damage because irreversible axonal lesions occurring at the onset of the disease have recently been reported. Testing of central motor tracts, in addition to visual, auditory, and somatosensory pathways, therefore appears appropriate in the multimodal assessment of pediatric patients with suspected multiple sclerosis.     

Chronic infantile neurological, cutaneous, and articular syndrome with severe early articular manifestations

We report an 11-month-old boy of French origin who had chronic, infantile, neurological, cutaneous, and articular syndrome with a particularly severe joint involvement with early onset. The diagnosis was based on the association of neurologic, cutaneous (urticarial skin eruption), and articular manifestations accompanied by recurrent bouts of fever. No mutation of the CIAS1 gene could be identified. Skeletal involvement was particularly severe, leading to considerable limitation of motion.     

AZD7762, a novel checkpoint kinase inhibitor, drives checkpoint abrogation and potentiates DNA-targeted therapies

Insights from cell cycle research have led to the hypothesis that tumors may be selectively sensitized to DNA-damaging agents resulting in improved antitumor activity and a wider therapeutic margin. The theory relies on the observation that the majority of tumors are deficient in the G1-DNA damage checkpoint pathway resulting in reliance on S and G2 checkpoints for DNA repair and cell survival. The S and G2 checkpoints are regulated by checkpoint kinase 1, a serine/threonine kinase that is activated in response to DNA damage; thus, inhibition of checkpoint kinase 1 signaling impairs DNA repair and increases tumor cell death. Normal tissues, however, have a functioning G1 checkpoint signaling pathway allowing for DNA repair and cell survival. Here, we describe the preclinical profile of AZD7762, a potent ATP-competitive checkpoint kinase inhibitor in clinical trials. AZD7762 has been profiled extensively in vitro and in vivo in combination with DNA-damaging agents and has been shown to potentiate response in several different settings where inhibition of checkpoint kinase results in the abrogation of DNA damage-induced cell cycle arrest. Dose-dependent potentiation of antitumor activity, when AZD7762 is administered in combination with DNA-damaging agents, has been observed in multiple xenograft models with several DNA-damaging agents, further supporting the potential of checkpoint kinase inhibitors to enhance the efficacy of both conventional chemotherapy and radiotherapy and increase patient response rates in a variety of settings.     

Postoperative control in deep brain stimulation of the subthalamic region: the contact membership concept

Object

In deep brain stimulation, the anatomic positions of electrode contact centers are used as the basis for analysis. We propose a new semi-quantitative approach (contact membership concept) considering patient’s individual anatomy, contact size, and extent of involvement of STN and neighboring structures.

Materials and methods

In ten bilaterally operated and improved Parkinsonian patients, effective contact positions (contacts used for monopolar stimulation) were analyzed. The position of the contact center (classical binary approach: each center assigned, 1, or not, 0, to a given structure) and of the contact in its dimension (contact membership concept: membership degree, ordinal values from 0 to 1, assigned to each anatomic structure according to extent of involvement) were compared for the whole patient group and, individually, for each patient.

Results

The membership concept revealed that for 13 out of 20 contacts, more than one structure was involved, where the classical binary approach assigned only one structure. For both approaches lateral STN, zona incerta and H1 (Forel’s Field) were the main structures involved, but their frequencies of appearance differed.

Conclusion

The membership concept allows detailed analysis of the anatomic contact position. In the future this approach could assist in correlating anatomy and clinical results for all electrode contacts (effective ones and clinically less efficient ones).     

Influence of early antioxidant supplements on clinical evolution and organ function in critically ill cardiac surgery, major trauma, and subarachnoid hemorrhage patients

Introduction

Oxidative stress is involved in the development of secondary tissue damage and organ failure. Micronutrients contributing to the antioxidant (AOX) defense exhibit low plasma levels during critical illness. The aim of this study was to investigate the impact of early AOX micronutrients on clinical outcome in intensive care unit (ICU) patients with conditions characterized by oxidative stress.

Methods

We conducted a prospective, randomized, double-blind, placebo-controlled, single-center trial in patients admitted to a university hospital ICU with organ failure after complicated cardiac surgery, major trauma, or subarachnoid hemorrhage. Stratification by diagnosis was performed before randomization. The intervention was intravenous supplements for 5 days (selenium 270 μg, zinc 30 mg, vitamin C 1.1 g, and vitamin B₁ 100 mg) with a double-loading dose on days 1 and 2 or placebo.

Results

Two hundred patients were included (102 AOX and 98 placebo). While age and gender did not differ, brain injury was more severe in the AOX trauma group (P = 0.019). Organ function endpoints did not differ: incidence of acute kidney failure and sequential organ failure assessment score decrease were similar (-3.2 ± 3.2 versus -4.2 ± 2.3 over the course of 5 days). Plasma concentrations of selenium, zinc, and glutathione peroxidase, low on admission, increased significantly to within normal values in the AOX group. C-reactive protein decreased faster in the AOX group (P = 0.039). Infectious complications did not differ. Length of hospital stay did not differ (16.5 versus 20 days), being shorter only in surviving AOX trauma patients (-10 days; P = 0.045).

Conclusion

The AOX intervention did not reduce early organ dysfunction but significantly reduced the inflammatory response in cardiac surgery and trauma patients, which may prove beneficial in conditions with an intense inflammation.

Trials Registration

Clinical Trials.gov RCT Register: NCT00515736.     

Endocannabinoid and serotonergic systems are needed for acetaminophen-induced analgesia

Acetaminophen is the most used analgesic/antipyretic drug. Its unclear mechanism of action could rely on cyclooxygenase inhibition, NO synthesis blockade or reinforcement of the serotonergic system. Here we show that in thermal, mechanical and chemical pain tests, AM-251, a specific CB(1) receptor antagonist, abolished the analgesic action of acetaminophen, which was also lost in CB(1) receptor knockout mice. Moreover, acetaminophen was shown unable to bind to CB(1) receptors demonstrating an indirect involvement of these receptors in the analgesic effect of this compound. Accordingly with these results, we also demonstrated that the inhibition of FAAH, an enzyme involved in the cerebral metabolism of acetaminophen into AM404, known to reinforce the activity of the endocannabinoid system, suppressed the antinociceptive effect of acetaminophen. In addition, similarly to the interaction of acetaminophen with bulbospinal serotonergic pathways and spinal serotonin receptors, we observed that the antinociceptive activity of ACEA, a CB(1) receptor agonist, was inhibited by lesion of bulbospinal serotonergic pathways and antagonists of spinal 5-HT receptors. We therefore propose that acetaminophen-induced analgesia could involve the following sequence: (1) FAAH-dependent metabolism of acetaminophen into AM404; (2) indirect involvement of CB(1) receptors by this metabolite; (3) endocannabinoid-dependent reinforcement of the serotonergic bulbospinal pathways, and (4) involvement of spinal pain-suppressing serotonergic receptors.     

An underrecognized source of organ donors: patients with brain death after successfully resuscitated cardiac arrest

Objective To identify predictors of brain death after successful resuscitation of out-of-hospital cardiac arrest (OHCA), with the goal of improving the detection of brain death, and to evaluate outcomes of solid organs harvested from these patients. Design and setting Prospective observational cohort study in a medical and surgical unit of a nonuniversity hospital. Patients Patients with successfully resuscitated OHCA were prospectively included in a database over a 7-year period. We looked for early predictors of brain death and compared outcomes of organ transplants from these patients to those from patients with brain death due to head injury or stroke. Results Over the 7-year period 246 patients were included. No early predictors of brain death were found. Of the 40 patients (16%) who met criteria for brain death, after a median ICU stay of 2.5 days (IQR 2.0–4.2), 19 donated 52 solid organs (29 kidneys, 14 livers, 7 hearts, and 2 lungs). Outcomes of kidneys and livers did not differ between donors with and without resuscitated cardiac arrest. Conclusions Brain death may occur in about one-sixth of patients after successfully resuscitated OHCA, creating opportunities for organ donation. C. A. received a grant from the publicly funded organization Agence de Biomédecine which manages organ donor data in France.