Feasibility of injected indocyanine green for ureteral identification during robotic left-sided colorectal resections.

BACKGROUND: Ureteral identification is essential to performing safe colorectal surgery. Injected immunofluorescence may aid with ureteral identification, but feasibility without ureteral catheterization is not well described. METHODS: Case series of robotic colorectal resections where indocyanine green (ICG) injection with or without ureteral catheter placement was performed. Imaging protocol, time to ureteral identification, and factors impacting visualization are reported. RESULTS: From 2019 to 2020, 83 patients underwent ureteral ICG injection, 20 with catheterization and 63 with injection only. Main indications were diverticulitis (52%) and cancer (36%). Median time to instill ICG was faster with injection alone than with catheter placement (4min vs 13.5min, p < 0.001). Median time [IQR] to right ureter (0.3 [0.01-1.2] min after robot docking) and left ureter (5.5 [3.1-8.8] min after beginning dissection) visualization was not different between injection alone and catheterization. CONCLUSION: ICG injection alone is faster than with indwelling catheter placement and equally reliable at intraoperative ureteral identification.

A case of isolated amyloid light-chain amyloidosis of the radial nerve.

Peripheral nerve involvement may be the first sign of systemic amyloid light-chain (AL) amyloidosis, a rare disease. Physical examination and electrodiagnostic testing are the mainstays of peripheral neuropathy evaluation at presentation. Sural nerve biopsy is performed in conjunction with serum and urine protein evaluation to differentiate between focal and systemic disease. Systemic disease is treated with a combination of chemotherapy, steroids, and stem cell transplantation. Isolated peripheral nerve disease is extremely rare. The authors here report the case of an 80-year-old woman who presented with progressive right upper-extremity weakness due to right radial neuropathy discovered upon electrodiagnostic testing. Magnetic resonance neurography (MRN) revealed a focal lesion within the right radial nerve. She underwent radial nerve exploration and excision of an intraneural mass consisting of amyloid on histopathology, with mass spectrometry analysis diagnostic for AL amyloidosis. Noninvasive testing and clinical history did not suggest systemic involvement. This unique case of isolated peripheral nerve AL amyloidosis in the absence of signs and symptoms of systemic disease is described, and the literature demonstrating peripheral nerve involvement in AL amyloidosis is reviewed.

Intraneural Granular Cell Tumor of a Cervical Dorsal Nerve Root: A Case Report and Review of the Literature.

BACKGROUND: Granular cell tumor (GCT) is a relatively uncommon predominantly benign lesion that usually presents as a solitary, painless cutaneous or submucosal nodule. Most of these tumors are found in the tongue. Although GCT is believed to have a Schwann cell origin, reports of GCT in peripheral and spinal nerves are uncommon. CASE DESCRIPTION: We report the case of a 43-year-old man with neck pain and hand numbness who was found to have a heterogeneously enhancing left-sided C2 nerve sheath tumor on magnetic resonance imaging. He underwent C2 decompression and resection of the left-sided C2 nerve sheath tumor with subsequent C1-C2 arthrodesis and instrumentation. Histopathologic review showed GCT. Review of the literature yielded 4 other reported cases of GCT within the vicinity of a spinal nerve root. Only one of these explicitly showed spinal nerve root involvement. This is a rare case of a GCT presenting as cervical nerve root mass, and what we believe is the first reported case of this in the literature. CONCLUSIONS: The surgeon should be aware of GCT when encountering spinal nerve root tumors because it may alter the surgical approach necessary for adequate resection compared with more commonly encountered nerve sheath tumors.

Synergistic Effects of Crizotinib and Temozolomide in Experimental FIG-ROS1 Fusion-Positive Glioblastoma.

Glioblastoma (GB) is the most common malignant brain tumor. Drug resistance frequently develops in these tumors during chemotherapy. Therefore, predicting drug response in these patients remains a major challenge in the clinic. Thus, to improve the clinical outcome, more effective and tolerable combination treatment strategies are needed. Robust experimental evidence has shown that the main reason for failure of treatments is signal redundancy due to coactivation of several functionally linked receptor tyrosine kinases (RTKs), including anaplastic lymphoma kinase (ALK), c-Met (hepatocyte growth factor receptor), and oncogenic c-ros oncogene1 (ROS1: RTK class orphan) fusion kinase FIG (fused in GB)-ROS1. As such, these could be attractive targets for GB therapy. The study subjects consisted of 19 patients who underwent neurosurgical resection of GB tissues. Our in vitro and ex vivo models promisingly demonstrated that treatments with crizotinib (PF-02341066: dual ALK/c-Met inhibitor) and temozolomide in combination induced synergistic antitumor activity on FIG-ROS1-positive GB cells. Our results also showed that ex vivo FIG-ROS1+ slices (obtained from GB patients) when cultured were able to preserve tissue architecture, cell viability, and global gene-expression profiles for up to 14 days. Both in vitro and ex vivo studies indicated that combination blockade of FIG, p-ROS1, p-ALK, and p-Met augmented apoptosis, which mechanistically involves activation of Bim and inhibition of survivin, p-Akt, and Mcl-1 expression. However, it is important to note that we did not see any significant synergistic effect of crizotinib and temozolomide on FIG-ROS1-negative GB cells. Thus, these ex vivo culture results will have a significant impact on patient selection for clinical trials and in predicting response to crizotinib and temozolomide therapy. Further studies in different animal models of FIG-ROS1-positive GB cells are warranted to determine useful therapies for the management of human GBs.

Chitosan reduces plasma adipocytokines and lipid accumulation in liver and adipose tissues and ameliorates insulin resistance in diabetic rats.

Chitosan is a natural product derived from chitin. To investigate the hypoglycemic and anti-obesity effects of chitosan, male Sprague-Dawley rats were divided into four groups: normal control, diabetic, and diabetic fed 5% or 7% chitosan. Diabetes was induced in rats by injecting streptozotocin/nicotinamide. After 10 weeks of feeding, the elevated plasma glucose, tumor necrosis factor-α, and interleukin-6 and lower adiponetin levels caused by diabetes were effectively reversed by chitosan treatment. In addition, 7% chitosan feeding also elevated plasma glucagon-like peptide-1 levels and lowered the insulin resistance index (homeostasis model assessment) in diabetic rats. Lower adipocyte granular intensities and higher lipolysis rates in adipose tissues were noted in the 7% chitosan group. Moreover, chitosan feeding reduced hepatic triglyceride and cholesterol contents and increased hepatic peroxisomal proliferator-activated receptor α expression in diabetic rats. Our results indicate that long-term administration of chitosan may reduce insulin resistance through suppression of lipid accumulation in liver and adipose tissues and amelioration of chronic inflammation in diabetic rats.

Biological monitoring of chlorpyrifos exposure to rice farmers in Vietnam.

Chlorpyrifos is the most common organophosphate insecticide registered for use in Vietnam and is widely used in agriculture, particularly rice farming. However, chlorpyrifos exposure to and adverse effects on farmers has not been evaluated. In this study, biological monitoring of chlorpyrifos exposure in a group of rice farmers was conducted after a typical application event using back-pack spraying. Urine samples (24 h) were collected from the rice farmers before and post insecticide application. Samples were analysed for 3,5,6-trichloropyridinol (TCP), the major urinary metabolite of chlorpyrifos, using an enzymatic pre-treatment before extraction followed by HPLC-MS/MS. Absorbed Daily Dose (ADD) of chlorpyrifos for farmers were then estimated from urinary TCP levels, expressed as µg g(-1)creatinine. The analytical method for urinary TCP had a low detection limit (0.6 µg L(-1)), acceptable recovery values (80-114%), and low relative percentage differences in duplicate and repeated samples. Post-application chlorpyrifos ADD of farmers varied from 0.4 to 94.2 µg kg(-1) (body weight) d(-1) with a mean of 19.4 µg kg(-1) d(-1) which was approximately 80-fold higher than the mean baseline exposure level (0.24 µg kg(-1) d(-1)). Hazard Quotients (ratio of the mean ADD for rice farmers to acute oral reference dose) calculated using acute oral reference doses recommended by United States and Australian agencies varied from 2.1 (Australian NRA), 4.2 (US EPA) to 6.9 (ATSDR). Biological monitoring using HPLC-MS/MS analysis of urinary TCP (24 h) was found to be an effective method for measuring chlorpyrifos exposure among farmers. This case study found that Vietnamese rice farmers had relatively high exposures to chlorpyrifos after application, which were likely to have adverse health effects.

Toxicokinetics, including saturable protein binding, of 4-chloro-2-methyl phenoxyacetic acid (MCPA) in patients with acute poisoning.

Human data on protein binding and dose-dependent changes in toxicokinetics for MCPA are very limited. 128 blood samples were obtained in 49 patients with acute MCPA poisoning and total and unbound concentrations of MCPA were determined. The Scatchard plot was biphasic suggesting protein binding to two sites. The free MCPA concentration increased when the total concentration exceeded 239mg/L (95% confidence interval 198-274mg/L). Nonlinear regression using a two-site binding hyperbola model estimated saturation of the high affinity binding site at 115mg/L (95%CI 0-304). Further analyses using global fitting of serial data and adjusting for the concentration of albumin predicted similar concentrations for saturable binding (184mg/L and 167mg/L, respectively) without narrowing the 95%CI. In 25 patients, the plasma concentration-time curves for both bound and unbound MCPA were approximately log-linear which may suggest first order elimination, although sampling was infrequent so zero order elimination cannot be excluded. Using a cut-off concentration of 200mg/L, the half-life of MCPA at higher concentrations was 25.5h (95%CI 15.0-83.0h; n=16 patients) compared to 16.8h (95%CI 13.6-22.2h; n=10 patients) at lower concentrations. MCPA is subject to saturable protein binding but the influence on half-life appears marginal.

Acute human self-poisoning with the N-phenylpyrazole insecticide fipronil--a GABAA-gated chloride channel blocker.

OBJECTIVE: Fipronil, a broad spectrum N-phenylpyrazole insecticide that inhibits GABAA-gated chloride channels, has been in use since the mid-1990s. A high affinity for insect compared to mammalian GABA receptors results in lower animal toxicity than other insecticides blocking this channel. To date, only two accidental cases of fipronil poisoning in humans have been published. CASE SERIES: We report seven patients with fipronil self-poisoning seen prospectively in Sri Lanka together with pharmacokinetics for four patients. Non-sustained generalized tonic-clonic seizures were seen in two patients (peak measured plasma fipronil concentrations 1600 and 3744 microg/L); both were managed with diazepam without complications. A patient with a peak measured plasma concentration of 1040 microg/L was asymptomatic throughout his stay. Plasma concentration was still high at discharge 3-4 days post-ingestion when the patients were well. Retrospective review of >1000 pesticide poisoning deaths since 1995 found only one death from fipronil-based products. In contrast to the good outcome of the above cases, this patient required intubation and ventilation and had continuous fits despite therapy with barbiturates and benzodiazepines. CONCLUSIONS: Our experience with prospectively observed patients suggests that fipronil poisoning is characterized by vomiting, agitation, and seizures, and normally has a favorable outcome. Management should concentrate on supportive care and early treatment of seizures. However, further experience is needed to determine whether increased susceptibility to fipronil or larger doses can produce status epilepticus.