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Aim: The aim was to investigate the RAS discordance between initial and recurrent metastasectomy specimens in metastatic colorectal cancer (mCRC) patients treated with chemotherapy (CT) plus biological agents in a first-line setting., Methods: Patients who had been treated with CT plus bevacizumab or cetuximab or panitumumab followed by R0 resection for potentially resectable colorectal cancer liver metastases were scanned. Among these, patients who developed resectable new metastases after a disease-free interval longer than 6 months were included in the study. We compared the RAS mutation status between the first biopsy and the second metastasectomy specimen., Results: A total of 82 mCRC patients treated with CT plus biological agents in a first-line setting were included in the study. The first biopsy assessment showed wild-type RAS tumours in 39 (47.6%) patients and mutant RAS tumours in 43 (52.4%) patients. The mean time for new operable liver metastasis after R0 resection was 15.5 months. In the second metastasectomy specimens, the numbers of wild-type and mutant RAS tumours were 30 (36.6%) and 52 (63.4%), respectively. The comparison with the first biopsy specimens showed RAS status conversions in 17 (20.7%) patients. Univariate comparison between patients with and without RAS status conversion revealed that grade, pathological T stage, wild-type RAS tumour and longer biological agent use time in the first-line treatment were significant factors for RAS conversion., Conclusion: Our results suggest that re-biopsy is needed for an optimal second-line treatment decision in mCRC patients regardless of backbone biological agent, especially in patients with wild-type RAS mCRC., (© 2020 The Association of Coloproctology of Great Britain and Ireland.)

Background: Clinical scoring systems have been used to reduce negative appendectomy rate for several decades. However, the use of these systems has been questioned due to differences in their diagnostic accuracies. The aim of this prospective study was to develop a new clinical scoring system using a combination of all previously described variables for the diagnosis of acute appendicitis (AA)., Methods: Consecutive patients who underwent emergency appendectomy for AA between December 2016 and April 2017 were prospectively included in the study. During admission, a prepared questionnaire including variables obtained from the previously used clinical scoring systems was administered. Histopathological analysis was regarded as the main outcome. Patients with no histopathological evidence of AA were defined as negative appendectomy. All variables were analyzed separately to assess their association with AA. A receiver operating characteristic curve with area under curve analysis was performed to obtain the cut-off values for numerical variables., Results: There were 200 patients with a mean age of 30.8±12.8 years with a negative appendectomy rate of 5.5%. There was no significant association between the variables and the detection of histologically proven AA except increased white blood cell count >11.05/mm3 and proportion of the polymorphonuclear leukocytes >71.2% (p=0.003 and p=0.015, respectively)., Conclusion: The present study shows that the development and/or use of scoring systems does not significantly improve the diagnostic accuracy of AA.

Background/purpose: Communicating bronchopulmonary foregut malformations (CBPFM) are a diverse group of potentially devastating congenital anomalies with anatomy that may be difficult to delineate. The authors present a case that illustrates conundrums in the diagnosis and management of these complex disorders., Methods: A term baby had esophageal atresia (EA), tracheoesophageal fistula (TEF), and tetralogy of Fallot. Initially, a gastrostomy was performed, and a balloon catheter was inserted through the endotracheal tube to occlude the fistula until the patient was hemodynamically stable. Subsequently, the fistula was ligated. Postoperatively, the left lung collapsed, and bronchoscopy showed an atretic left mainstem bronchus. Repeat thoracotomy showed that the fistula ligation was intact. Air was introduced through the gastrostomy tube, and, surprisingly, the left lung inflated, indicating the left mainstem bronchus arose from the esophagus distal to the ligated TEF., Results: Despite reopening this fistula, ventilation remained poor, and support was withdrawn. Autopsy findings confirmed a unilobed left lung arising from the esophagus, EA, TEF, an atretic left mainstem bronchus, tetralogy of Fallot, and DiGeorge syndrome., Conclusions: This is the first report of a combination of EA and distal TEF with a second CBPFM involving the esophagus and the entire left lung. Successful correction of these anomalies will require extensive delineation of the anatomy to plan an operative strategy.

Herpes simplex virus vectors bearing a glucose transporter (GT) gene and a marker gene were found to protect neurons against a 1-h focal ischemic insult. Rats receiving the GT vector v alpha22beta gal alpha4GT exhibited a 67.4 +/- 35.3% survival of virally targeted neurons in the ischemic hemisphere compared with the contralateral control (n = 7), whereas rats receiving a control vector exhibited only 32.8 +/- 17.9% survival (n = 9). This significant improvement in survival (105%, p=0.022) suggests that energy failure is an important contributor to the neuropathology of ischemic damage in the striatum, and that it can be alleviated by gene transfer. This is the first demonstration of protection against ischemic cerebral injury by the direct transfer of GT genes to neurons.

Because neurons are postmitotic, they are irreplaceable once they succumb to necrotic insults such as hypoglycemia, ischemia, and seizure. A paucity of energy can exacerbate the toxicities of these insults; thus, a plausible route to protect neurons from necrotic injury would be to enhance their glucose uptake capability. We have demonstrated previously that defective herpes simplex virus (HSV) vectors overexpressing the rat brain glucose transporter (GT) gene (gt) can enhance glucose uptake in adult rat hippocampus and in hippocampal cultures. Furthermore, we have observed that such vectors can maintain neuronal metabolism during hypoglycemia and reduce kainic acid-induced seizure damage. In this study, we have developed bicistronic vectors that coexpressed gt and Escherichia coli lacZ as a reporter gene, which allows us to identify directly neurons that are infected with the vectors. Overexpression of GT from these vectors protected cultured hippocampal, spinal cord, and septal neurons against various necrotic insults, including hypoglycemia, glutamate, and 3-nitropropionic acid. Our observations demonstrate the feasibility of using HSV vectors to protect neurons from necrotic insults. Although this study has concentrated on the delivery of gt, other genes with therapeutic or protective capability might also be used.

With its natural propensity to infect and establish life-long latency in neurons, herpes simplex virus type 1 (HSV-1) has been successfully employed by various laboratories as vectors for gene transfer into neurons. However, analysis of its cytopathic effects in vivo and in vitro has been limited. In this study, we examined the cytopathic effects of 2 HSV-1 alpha 4 mutants (ts756 and d120) on adult rat hippocampus and striatum and of d120 on hippocampal neurons in culture. We assessed damage by stringent counting of surviving neurons after infection and demonstrated that while neither ts756 nor d120 infection resulted in any gross anatomical or behavioral changes of the animals, ts756, but not d120, produced a significant amount of damage in the CA4 cell field and dentate gyrus of the hippocampus. Thus, since crude examination is insufficient to detect subtle but significant degrees of neuron loss, the cytopathic effects of HSV or any vector system must be carefully analyzed. Furthermore, we also observed that uninfected cell lysates damaged neurons, both in vivo and in vitro. This cytotoxicity occurred within the first 24 h post-inoculation and probably arose through the activation of glutamate receptors. For the preparation of HSV vectors, purification of the virus from soluble cellular components by a simple pelleting step can significantly decrease such acute toxicity.