Feasibility and safety of irreversible electroporation (IRE) in patients with small renal masses: Results of a prospective study

Background

Irreversible electroporation (IRE) has the potential to overcome limitations of thermal ablation, enabling small renal mass (SRM) ablation near vital structures.

Elevated fluoride products enhance remineralization of advanced enamel lesions

Caries prevention might benefit from the use of toothpastes containing over 1500 ppm F. With few clinical studies available, the aim of this pH-cycling study was to investigate the dose response between 0 and 5000 ppm F of de- and remineralization of advanced (> 150 microm) enamel lesions. Treatments included sodium and amine fluoride, and a fluoride-free control. Mineral uptake and loss were assessed from solution calcium changes and microradiographs. Treatments with 5000 ppm F both significantly enhanced remineralization and inhibited demineralization when compared with treatments with 1500 ppm F. Slight differences in favor of amine fluoride over sodium fluoride were observed. The ratio of de- over remineralization rates decreased from 13.8 to 2.1 in the range 0 to 5000 ppm F. As much as 71 (6)% of the remineralized mineral was calculated to be resistant to dissolution during subsequent demineralization periods. With 5000-ppm-F treatments, more demineralizing episodes per day (10 vs. 2 for placebo) would still be repaired by remineralization.     

ASO Visual Abstract: Metastasectomy or Stereotactic Body Radiation Therapy With or Without Systemic Therapy for Oligometastatic Esophagogastric Cancer

Annals of Surgical Oncology -     

Cerebral blood flow pattern and autoregulation during open-heart surgery in infants and young children: a transcranial, Doppler ultrasound study.

OBJECTIVES: To elucidate the effect of cardiopulmonary bypass on cerebral perfusion and on the autoregulatory ability of the cerebral vascular bed of infants and young children. SETTING: Operating room. DESIGN: Prospective study. PATIENTS: Thirteen newborn infants and young children undergoing open-heart surgery. INTERVENTIONS: Cerebral blood flow velocity was monitored in the patients undergoing open-heart surgery from just before the induction of anesthesia until the discontinuation of anesthesia after completion of the surgery. MEASUREMENTS AND MAIN RESULTS: Cerebral blood flow velocity was assessed by semicontinuous measurement of temporal mean blood flow velocity in the middle cerebral artery using a range-gated, pulsed Doppler flowmeter with a transducer that was firmly attached to the left temporal region of the head. Mean arterial pressure (MAP) and nasopharyngeal temperature were continuously monitored. During hypothermic (18.4 degrees C to 31.9 degrees C) cardiopulmonary bypass, cerebral blood flow velocity decreased and showed a close relationship with nasopharyngeal temperature (p less than .0001). During steady-state cardiopulmonary bypass, cerebral blood flow velocity showed a correlation with MAP (p less than .01). The nasopharyngeal temperature influenced this relationship: at lower (absolute) nasopharyngeal temperatures, lack of cerebral autoregulation was more common. CONCLUSIONS: The finding suggests that cerebral blood flow decreases with decreasing nasopharyngeal temperature. During hypothermic cardiopulmonary bypass, cerebral autoregulation seems to be easily disturbed, especially at low nasopharyngeal temperatures.     

Spontaneous Tumor Regression in a Syngeneic Rat Model of Liver Cancer: Implications for Survival Studies

PurposeTo characterize tumor growth of N1S1 cells implanted into the liver of Sprague–Dawley rats to determine if this model could be used for survival studies. These results were compared with tumor growth after implantation with McA-RH7777 cells.Materials and MethodsN1S1 or McA-RH7777 cells were implanted into the liver of Sprague–Dawley rats (n = 20 and n = 12, respectively) using ultrasound (US) guidance, and tumor growth was followed by using US. Serum profiles of 19 cytokines were compared in naive versus tumor-bearing rats.ResultsBoth types of tumors were visible on US 1 week after tumor implantation, but the mean tumor volume of N1S1 tumors was larger compared to McA-RH7777 tumors (231 mm³ vs 82.3 mm³, respectively). Tumor volumes in both groups continued to increase, reaching means of 289 mm³ and 160 mm³ in N1S1 and McA-RH7777 groups, respectively, 2 weeks after tumor implantation. By week 3, tumor volumes had decreased considerably, and six tumors (50%) in the McA-RH7777 had spontaneously regressed, versus two (10%) in the N1S1 group. Tumor volumes continued to decrease over the following 3 weeks, and complete tumor regression of all tumors was seen 5 weeks and 6 weeks after tumor implantation in the McA-RH7777 and N1S1 groups, respectively. In an N1S1-implanted rat, multiple cytokines that have been shown to correlate with the ability of the tumor to survive in a hostile environment were increased by as much as 50%, whereas the average increase in cytokine levels was 90%. These findings suggest that the net cytokine environment favors an antitumor immune response. A similar trend was observed in a rat with a McA-RH7777 tumor, and the increase in cytokine levels was considerably more pronounced, with an average increase of 320%.ConclusionsThe model of N1S1 cell implantation in the liver of Sprague–Dawley rats is not ideal for survival studies and should only be used with great caution in short-term studies that involve cancer therapies.     

Neuroanatomical evidence demonstrating the existence of the vagal anti-inflammatory reflex in the intestine

Background The cholinergic anti‐inflammatory pathway is proposed to be part of the so‐called vago‐vagal ‘inflammatory reflex’. The aim of this study is to provide neuro‐anatomical evidence to support the existence of a functional neuronal circuit and its activation in response to intestinal inflammation. Methods The expression of c‐fos was evaluated at different levels of the neurocircuitry in the course of postoperative ileus (POI) in a mouse model. Specific activation of the motor neurons innervating the inflamed intestine and the spleen was monitored by retrograde tracing using cholera toxin‐b. The role of the vagal afferent pathway nerve was evaluated by selective vagal denervation of the intestine. Key Results Abdominal surgery resulted in subtle inflammation of the manipulated intestine at 24 h (late phase), but not after 2 and 6 h (early) after surgery. This local inflammation was associated with activation of neurons in the nucleus of the solitary tract and in the dorsal nucleus of the vagus. The vagal output mainly targeted the inflamed zone: 42% of motor neurons innervating the intestine expressed c‐fos IR in contrast to 7% of those innervating the spleen. Vagal denervation of the intestine abolished c‐fos expression in the brain nuclei involved in the neuronal network activated by intestinal inflammation. Conclusions & Inferences Our data demonstrate that intestinal inflammation triggers a vagally mediated circuit leading mainly to activation of vagal motor neurons connected to the inflamed intestine. These findings for the first time provide neuro‐anatomical evidence for the existence of the endogenous ‘inflammatory reflex’ and its activation during inflammation.     

Recombinant Immunomodulating Lentogenic or Mesogenic Oncolytic Newcastle Disease Virus for Treatment of Pancreatic Adenocarcinoma

Oncolytic Newcastle disease virus (NDV) might be a promising new therapeutic agent for the treatment of pancreatic cancer. We evaluated recombinant NDVs (rNDVs) expressing interferon (rNDV-hIFNβ-F₀) or an IFN antagonistic protein (rNDV-NS1-F₀), as well as rNDV with increased virulence (rNDV-F_3aa) for oncolytic efficacy in human pancreatic adenocarcinoma cells. Expression of additional proteins did not hamper virus replication or cytotoxic effects on itself. However, expression of interferon, but not NS1, resulted in loss of multicycle replication. Conversely, increasing the virulence (rNDV-F_3aa) resulted in enhanced replication of the virus. Type I interferon was produced in high amounts by all tumor cells inoculated with rNDV-hIFNβ-F₀, while inoculation with rNDV-NS1-F₀ resulted in a complete block of interferon production in most cells. Inoculation of human pancreatic adenocarcinoma cells with rNDV-F_3aa caused markedly more cytotoxicity compared to rNDV-F₀, while inoculation with rNDV-hIFNβ-F₀ and rNDV-NS1-F₀ induced cytotoxic effects comparable to those induced by the parental rNDV-F₀. Evaluation in vivo using mice bearing subcutaneous pancreatic cancer xenografts revealed that only intratumoral injection with rNDV-F_3aa resulted in regression of tumors. We conclude that although lentogenic rNDVs harboring proteins that modulate the type I interferon pathway proteins do have an oncolytic effect, a more virulent mesogenic rNDV might be needed to improve oncolytic efficacy.     

"Diabetes of the elderly" and type 2 diabetes in younger patients: possible role of the biological clock

The increased prevalence of type 2 diabetes in the aged has been recognized for a long time. Within the last decades, a growing number of younger subjects and even children are prone to develop type 2 diabetes. In both groups, aged and young, the biological clock, located in the suprachiasmatic nucleus of the hypothalamus (SCN) is malfunctioning as evidenced by disturbed sleep cycles and altered circadian rhythms. While elderly patients have an impaired function of the SCN due to the degeneration of neurons, we propose that in younger subjects the clock loses its "feeling" for internal and external rhythms caused by the modern lifestyle. Sleeping late and less coupled with constant metabolic excess alter both internal and external environmental stimuli to the brain. In response to these alterations, the rhythm of the biological clock is disrupted which may lead to the metabolic syndrome and type 2 diabetes.     

Non‐alcoholic fatty liver disease as a consequence of autonomic imbalance and circadian desynchronization

The circadian system, headed by the suprachiasmatic nucleus, synchronizes behaviour and metabolism according to the external light–dark cycle through neuroendocrine and autonomic signals. Metabolic diseases, such as steatosis, obesity and glucose intolerance, have been associated with conditions of circadian misalignment wherein the feeding schedule has been moved to the resting phase. Here we describe the physiological processes involved in liver lipid accumulation and show how they follow a circadian pattern importantly regulated by both the autonomic nervous system and the feeding–fasting cycle. We propose that an unbalanced activity of the sympathetic–parasympathetic branches between organs induced by circadian misalignment provides the conditions for the development and progression of non‐alcoholic fatty liver disease.     

Trends in Nontherapeutic Laparotomy Rates in Patients Undergoing Surgical Therapy for Hepatic Colorectal Metastases

Surgery is the treatment of choice in selected patients with hepatic colorectal metastases. Despite improvements in preoperative imaging, patients can undergo unnecessary nontherapeutic laparotomy. The aim of this study was to examine trends in nontherapeutic laparotomy rates in patients undergoing planned surgical therapy for hepatic colorectal metastases. Data from 530 operations (461 patients) undergoing potentially curative surgical therapy for colorectal liver metastases between 1994 and 2005 were analyzed. The incidence of nontherapeutic laparotomy was determined and factors associated with nontherapeutic laparotomy were identified. Overall, 49 nontherapeutic laparotomies were performed (9.2%). Higher nontherapeutic laparotomy rates were seen in patients with multiple metastases and tumor size >5 cm (both P < 0.05). Preoperative positron emission tomography (PET) imaging was associated with lower risk of nontherapeutic laparotomy [5.6% versus 12.4%, P = 0.009, odds ratio (OR) = 0.42]. At laparotomy, extrahepatic findings were the reason for nontherapeutic laparotomy in 44.9% of cases. The nontherapeutic laparotomy rate significantly decreased over time (14.9% for 1994–1997 versus 9.6% for 1998–2001 versus 4.7% for 2002–2005; P = 0.003). While patients in each time period were similar with regard to tumor specific factors, utilization of PET imaging (P < 0.001) as well as resection plus ablation (P = 0.004) increased over time. We conclude that prevalence of nontherapeutic laparotomy for patients undergoing surgical exploration for hepatic colorectal metastases has decreased significantly in recent years to less than 5%. The reasons for this trend are probably multifactorial and may include improved preoperative assessment, such as PET imaging, as well as salvage surgical options.