Surgeon-Dependent Variability in Cost of Gastrointestinal Operations in a Single Cancer Center.

INTRODUCTION: Cancer operations are increasingly utilizing specialized equipment and technology. Related costs are often not known to the responsible surgeon. We seek to evaluate cost aspects of care episodes attributable to the surgeon's management decisions. METHODS: Financial cost data in a tertiary academic cancer center were queried over 3 y. Consecutive patients undergoing gastrointestinal operations followed by inpatient admission of two or more days were included, excluding patients with 40+ d admissions. Analysis of variance, Kruskal-Wallis, and multiple regression statistics were utilized. RESULTS: The study population included 1540 patients: 54% men and 46% women, with a median age of 64 y (range 15-95). Eight surgeons conducted major (82%) and minor (18%) operations, with a minimally invasive surgical approach in 60.4%. Procedures included colorectal (37%), pancreatic (19%), esophagogastric (18%), hepatobiliary (18%), and small bowel resections (8%). Total direct costs differed between surgeons with an analysis of variance coefficient range between -$3265 and +$6163 (P < 0.001). Surgeons' cost differences were observed for central medical supply, operating room (OR) supply, total OR, inpatient room, laboratory, pharmacy, supportive care (P < 0.001), and radiology costs (P < 0.02). OR supply cost was the dominant consistent domain with significant differences between surgeons in all case subcategories. When controlled for case category and minimally invasive surgical approach, multiple regression showed the most significant variations between surgeons in ORs, medical supply, and nutrition costs (P < 0.001), followed by laboratory costs (P < 0.01). Top OR supply costs were staplers and energy devices. CONCLUSIONS: Even in a highly subspecialized surgical environment, surgeons' variable utilization of ORs and medical supplies is strongly linked to variations in care-related costs. Specific queries into supply items should reduce costs and optimize value generated.

Perioperative Chemotherapy is Associated with Superior Overall Survival in Patients with Synchronous Colorectal Liver Metastases.

BACKGROUND: The sequence of localized and systemic treatment for colorectal liver metastases (CRLM) remains debated. Our objective is to analyze the effect of treatment sequence on overall survival (OS) in patients with CRLM using a large cancer database. PATIENTS AND METHODS: The national cancer database (NCDB) was utilized to identify patients with stage IV colorectal cancer (CRC) diagnosed between 2004 and 2016. OS was analyzed using standard univariate and multivariate methods. RESULTS: We identified 72,376 patients with synchronous CRLM, of whom 43,039 had liver-only metastases. Patients with liver-only CRLM had a median OS of 18.9 months, versus those with CRLM plus extrahepatic sites (11.3 months). In patients with liver-only CRLM, resection of both the primary and metastatic site was associated with median OS 38.9 months versus 30.2 months after resection of the metastatic site alone, and resection of the primary tumor alone (22.3 months, all p < 0.001). Receipt of perioperative chemotherapy correlated with a median OS of 44.7 months versus preoperative chemotherapy only (38.4 months) or postoperative chemotherapy only (27.9 months, all p < 0.001). Patients who received chemotherapy alone had a median OS of 16.4 months versus those who underwent resection without chemotherapy (9.5 months, p < 0.001). CONCLUSIONS: This study reveals a correlation between perioperative chemotherapy and superior OS in patients with liver-only CRLM, and shows that resection of the metastatic site was linked to better OS. Despite obvious cohort heterogeneity, the data can support a resection approach with additional, preferably peri- or preoperative systemic therapy for patients with CRLM.

Conjugated Bile Acids Accelerate Progression of Pancreatic Cancer Metastasis via S1PR2 Signaling in Cholestasis.

BACKGROUND: Pancreatic cancer (PC) has an extremely high mortality rate, where obstructive jaundice due to cholestasis is a classic symptom. Conjugated bile acids (CBAs) such as taurocholic acid (TCA) have been reported to activate both the ERK1/2 and AKT signaling pathways via S1P receptor 2 (S1PR2) and promote growth of cholangiocarcinoma. Thus, we hypothesize that CBAs, which accumulate in cholestasis, accelerate PC progression via S1PR2. METHODS: Murine Panc02-luc and human AsPC-1, MIA PaCa2, and BxPC-3 cells were treated with TCA, S1PR2 agonist CYM5520, S1PR2 antagonist JTE-013, sphingosine-1-phosphate (S1P), and functional S1P receptor antagonist (except S1PR2) FTY720. Bile duct ligation (BDL) was performed on liver implantation or intraperitoneal injection of Panc02-luc cells. RESULTS: Panc02-luc and AsPC-1 cells predominantly expressed S1PR2, and their growth and migration were stimulated by TCA or CYM5520 in dose-dependent manner, which was blocked by JTE-013. This finding was not seen in PC cell lines expressing other S1P receptors than S1PR2. Panc02-luc growth stimulation by S1P was not blocked by FTY720. BDL significantly increased PC liver metastasis compared with sham. PC peritoneal carcinomatosis was significantly worsened by BDL, confirmed by number of nodules, tumor weight, bioluminescence, Ki-67 stain, ascites, and worse survival compared with sham. CYM5520 significantly worsened PC carcinomatosis, whereas treatment with anti-S1P antibody or FTY720 also worsened progression. CONCLUSIONS: CBAs accelerated growth of S1PR2 predominant PC both in vitro and in vivo. This finding implicates S1PR2 as a potential therapeutic target in metastatic S1PR2 predominant pancreatic cancer.

An eco-friendly route of γ-Fe2O3 nanoparticles formation and investigation of the mechanical properties of the HPMC-γ-Fe2O3 nanocomposites.

In recent times, biosynthetic approaches toward the synthesis of nanoparticles have been shown to have several advantages over physical and chemical methods. Here, we report the extracellular mycosynthesis of γ-Fe2O3 nanoparticles by Alternaria alternata. The fungal biomass when exposed to aqueous iron(III) chloride solution led to the formation of highly stable γ-Fe2O3 nanoparticles extracellularly. The influence of these biosynthesized γ-Fe2O3 nanoparticles on the properties of hydroxyl propyl methyl cellulose was also investigated. Characterization of the biosynthesized γ-Fe2O3 nanoparticles and HPMC-γ-Fe2O3 nanocomposite films were done by the different types of spectral and electron microscopic analysis. The size of the γ-Fe2O3 nanoparticles ranges from 75 to 650 nm. The mechanical effect of the agglomerated γ-Fe2O3 nanoparticles into the HPMC polymer matrix was also investigated.

Bow hunter's syndrome causing vertebrobasilar insufficiency in a young man with neck muscle hypertrophy.

Vertebrobasilar insufficiency is characterized by impaired blood flow within the posterior circulation, producing symptoms of vertigo, nausea, vomiting, visual disturbances, and syncope. Given these nonspecific symptoms, the diagnosis of vertebrobasilar ischemia may be difficult to distinguish from more benign conditions. A healthy 37-year-old man presented to our clinic with near syncope upon turning his head to the left. Dynamic angiography revealed occlusion of the left vertebral artery at C7 with 90° head rotation to the left, consistent with bow hunter's syndrome. No obvious bony abnormalities were identified on computed tomography or magnetic resonance imaging scans. Transient rotational vertebral artery syndrome, a rare cause of vertebrobasilar insufficiency, has most often been reported at the C1-2 level, and the majority of cases occur in patients >50 years of age because of degenerative osteophytes and contralateral atherosclerosis. We present the unusual case of a young man with symptoms of vertebrobasilar insufficiency and discuss the potential effects of weightlifting and neck muscle hypertrophy on vertebral artery flow dynamics.

Biosynthesis and safety evaluation of ZnO nanoparticles.

The secrets gleaned from nature have led to the development of biomimetic approaches for the growth of advanced nanomaterials. Biological methods for nanoparticle synthesis using microorganisms, enzymes, and plants or plant extracts have been suggested as possible ecofriendly alternatives to chemical and physical methods. Here, we report extracellular mycosynthesis of ZnO-NPs by Alternaria alternata (Fr.) Keissl (1912). On treating zinc sulfate solution with fungal culture filtrate, rapid reduction of ZnSO4 was observed leading to the formation of highly stable ZnO-NPs in the solution and up-to-date literature survey showed this was the first report of biosynthesis of ZnO-NPs using this fungus. The particles thereby obtained were characterized by different analytical techniques. EDX-spectrum revealed the presence of zinc and oxygen in the nanoparticles. FTIR spectroscopy confirmed the presence of a protein shell outside the nanoparticles which in turn also support their stabilization. DLS and TEM analysis of the ZnO-NPs indicated that they ranged in size from 45 to 150 nm with average size of 75 ± 5 nm. But potential negative impacts of nanomaterials are sometimes overlooked during the discovery phase of research. Therefore, in the present study, bio-safety of mycosynthesized ZnO-NPs were evaluated by using cytotoxicity and genotoxicity assays in human lymphocyte cells, in vitro. Cytotoxicity studied as function of membrane integrity and mitochondrial dehydrogenase activity revealed significant (P < 0.05) toxicity at treatment concentration of 500 µg/ml and above. Additionally, DNA damaging potential was also studied using comet assay. The results revealed significant genotoxicity at the highest concentration (1,000 µg/ml).

Spinster Homologue 2 Expression Correlates With Improved Patient Survival in Hepatocellular Carcinoma Despite Association With Lymph-Angiogenesis.

Background: Spinster homologue 2 (SPNS2) is a transporter of sphingosine-1-phosphate (S1P), a bioactive lipid linked to cancer progression. We studied the link between SPNS2 gene expression, tumor aggressiveness, and outcomes in patients with hepatocellular carcinoma (HCC). Methods: Gene expression in patients with HCC was analyzed from the Cancer Genome Atlas (TCGA) (n = 350) and GSE76427 (n = 115) as a validation cohort, as well as liver tissue cohort GSE6764 (n = 75). Results: High-SPNS2 HCC was significantly associated with high level of lymph-angiogenesis-related factors. SPNS2 expression was significantly higher in normal liver and early HCC versus advanced HCC (P < 0.02). High SPNS2 levels enriched immune response-related gene sets; inflammatory, interferon (IFN)-α, IFN-γ responses, and tumor necrosis factor (TNF)-α, interleukin (IL)-6/Janus kinase/signal transducer and activator of transcription (JAK/STAT3) signaling, complement and allograft rejection, but did not significantly infiltrate specific immune cells nor cytolytic activity score. High-SPNS2 HCC enriched tumor aggravating pathway gene sets such as KRAS (Kirsten rat sarcoma virus) signaling, but inversely correlated with Nottingham histological grade, MKI67 (marker of proliferation Ki-67) expression, and cell proliferation-related gene sets. Further, high-SPNS2 HCC had significantly high infiltration of stromal cells, showing that low-SPNS2 HCC is highly proliferative. Finally, high-SPNS2 HCC was associated with better disease-free, disease-specific, and overall survival (P = 0.031, 0.046, and 0.040, respectively). Conclusions: Although SPNS2 expression correlated with lymph-angiogenesis and other cancer-promoting pathways, it also enriched immune response. SPNS2 levels were higher in normal liver compared to HCC, and inversely correlated with cancer cell proliferation and better survival. SPNS2 expression may be beneficial in HCC patients despite detrimental in-vitro effects.

Role of vasopressin in maintenance of potassium homeostasis in severe hemorrhage.

Uncontrolled elevation in plasma potassium within minutes of rapid blood volume loss is associated with mortality and distinguishes nonsurvivors of severe hemorrhage from survivors. In a pig model of severe hemorrhage, we discovered that along with a sharp increase in plasma potassium coincident with a shut down of urine flow, nonsurvivors also had an insufficient vasopressin response to hemorrhage. In contrast, survivors did have elevated vasopressin levels in response to hemorrhage and maintained plasma potassium within normal limits. While it has been demonstrated for some time that vasopressin can influence secretion of potassium in the distal nephron, the magnitude of this effect and conditions under which this contributes to physiological modulation of potassium excretion has yet to be defined. In this review, we assess the evidence that would suggest that vasopressin plays a key role in modulating potassium excretion and is important in the regulation of potassium homeostasis during hemorrhage.

Bilateral adrenal hemorrhage after pancreaticoduodenectomy.

The incidence of bilateral adrenal hemorrhage (BAH) in the postoperative setting is rare, but potentially life threatening. A literature review of postoperative BAH reveals that there is limited data on BAH following abdominal surgery. We present a case of BAH following pancreaticoduodenectomy, which has not been previously documented in the literature. A 70-year-old male patient with no previous history of adrenal disease underwent an uncomplicated pancreaticoduodenectomy and was discharged after a typical postoperative course. He was readmitted with abdominal pain and ileus on POD 8 and a computed tomography (CT) scan was initially unremarkable, but a repeat CT scan on POD 11 demonstrated BAH. He was found to have adrenal insufficiency and was successfully treated with steroids. Clinicians should be aware of the possibility of adrenal hemorrhage postoperatively as it can potentially be a fatal surgical complication. To enhance patient outcomes, early detection and appropriate treatment are essential.

Low incisional hernia incidence using a large-bite, low-tension technique for celiotomy closure.

Background: Incisional herniae (IH) are reported in 5->20 % of patients undergoing open celiotomy, and can be linked to closure technique. The STITCH randomized trial favors a small bite technique for midline celiotomy closure with a 1-year IH rate of 13 % over larger bites (23 %). Methods: A continuous musculofascial mass closure with absorbable looped #1 PDS suture with 2-cm bite size was used for all open celiotomies. IH frequency and associated clinicopathologic factors were retrospectively analyzed from prospective data in 336 consecutive patients undergoing visceral resections by a single surgeon. Results: The study population included 192 men and 144 women, 81 % of whom had a cancer diagnosis, who underwent hepatobiliary, pancreatic, gastroesophageal, and colorectal resections, or a combination. The majority of patients (84 %) had subcostal incisions, and 10 % received a midline incision. At a median follow-up of 19.5 months, the overall IH rate was 3.3 %. Hernia rates were 2.5 % for subcostal margin, 2.9 % for midline, and 5.5 % for other incisions (p = 0.006). Median time to hernia detection was 492 days. Factors associated with IH were increased weight, abdominal depth/girth, male sex, spleen size, visceral fat, and body height (p ≤ 0.04 for all), but not type of resection, prior operations, underlying diagnosis, weight loss, adjuvant chemotherapy or radiation, incision length or suture to incision ratio. Conclusions: The described technique leads to a low IH rate of <3 % in subcostal or midline incisions, and can be recommended for routine use. The observed results appear superior to those of the STITCH trial, even for the smaller midline incision cohort.

A State-of-the-Art Systemic Review on Selenium Nanoparticles: Mechanisms and Factors Influencing Biogenesis and Its Potential Applications.

Selenium is a trace element required for the active function of numerous enzymes and various physiological processes. In recent years, selenium nanoparticles draw the attention of scientists and researchers because of its multifaceted uses. The process involved in chemically synthesized SeNPs has been found to be hazardous in nature, which has paved the way for safe and ecofriendly SeNPs to be developed in order to achieve sustainability. In comparison to chemical synthesis, SeNPs can be synthesized more safely and with greater flexibility utilizing bacteria, fungi, and plants. This review focused on the synthesis of SeNPs utilizing bacteria, fungi, and plants; the mechanisms involved in SeNP synthesis; and the effect of various abiotic factors on SeNP synthesis and morphological characteristics. This article discusses the synergies of SeNP synthesis via biological routes, which can help future researchers to synthesize SeNPs with more precision and employ them in desired fields.

Fluctuations in Gut Microbiome Composition During Immune Checkpoint Inhibitor Therapy.

Background: Immune checkpoint inhibitors (ICIs) such as programmed cell death protein-1 (PD-1) inhibitors or PD-1 ligand-1 (PD-L1) inhibitors have led to remarkable improvement in outcomes of non-small cell lung cancer (NSCLC). Unfortunately, the significant benefits of ICI therapy are frequently limited by resistance to treatment and adverse effects, and the predictive value of pre-treatment tumor tissue PD-L1 expression is limited. Development of less invasive biomarkers that could identify responders and non-responders in early on-treatment could markedly improve the treatment regimen. Accumulating evidence suggests that baseline gut microbiota profile is associated with response to PD-1/PD-L1 blockade therapy. However, change in the gut microbiome composition during PD-1/PD-L1 blockade therapy and its relation to response remain unclear. Methods: Here, we analyzed pre- and on-treatment fecal samples from five NSCLC patients receiving anti-PD-1 immunotherapy, alone or in tandem with chemotherapy, and performed 16S rRNA sequencing. Results: The overall alpha diversity of the baseline gut microbiome was similar between three responders and two non-responders. While the gut microbiome composition remained stable overall during treatment (R2 = 0.145), responders showed significant changes in microbiome diversity between pre- and on-treatment samples during anti-PD-1 therapy compared to non-responders (P = 0.0274). Within the diverse microbiota, responders showed decreases in the abundance of genera Odoribacter, Gordonibacter, Candidatus Stoquefichus, Escherichia-Shigella, and Collinsella, and increase in abundance of Clostridium sensu stricto 1. In contrast, non-responders demonstrated on-treatment increases in genera Prevotella, Porphyromonas, Streptococcus, and Escherichia-Shigella, and decrease in abundance of Akkermansia. Conclusions: This pilot study identified a substantial change in gut microbiome diversity between pre- and on-treatment samples in NSCLC patients responding to anti-PD-1 therapy compared to non-responders. Our findings highlight the potential utility of gut microbiota dynamics as a noninvasive biomarker to predict response to PD-1/PD-L1 blockade therapy for a wide variety of malignancies, which sets a path for future investigation in larger prospective studies.

"Evaluation of physico-mechanical properties of naturally dyed betel-nut leaf plate (BLPF) - Banana blended fabric".

Betel-nut leaf plate fiber (BLPF) is a lingo-cellulosic natural fiber that can be used to make eco-friendly and biodegradable blended or hybrid fabric with Banana fiber. In the world of organic textiles, naturally dyed BLPF-Banana fiber can be used for wearable products and satisfy health and hygiene issues. BLPF and Banana fiber can be good natural fibers for hybrid fabrics despite being considered waste materials. In this research work, both of the fibers were pretreated carefully to get the desired fineness, color, flexibilities, etc., which are necessary to manufacture fabric. BLPF-Banana woven (1 × 1) hybrid fabric was developed where 12 Ne Banana yarns were used in the warp direction, and 20 Ne BLPF yarns were used in the weft direction and it was dyed naturally with Turmeric. Evaluations of different physico-mechanical properties; tensile strength (854.9 N), tearing strength (14.5 N), stiffness (3.1 N), crease recovery (75° angle), and fabric thickness (1.33 mm) of naturally dyed BLPF-Banana blended fabric were tested, and found satisfactory. SEM, FTIR, and Water vapor transmission tests were also conducted in this study. It attempted to turn the wastages into an asset to make a unique biodegradable BLPF-Banana hybrid fabric by blending two types of natural fibers with the help of natural dyeing substance; it could be a god replacement for synthetic blended fabric.

Predictive and Prognostic Implications of Circulating CX3CR1+ CD8+ T Cells in Non-Small Cell Lung Cancer Patients Treated with Chemo-Immunotherapy.

Lack of reliable predictive biomarkers is a major limitation of combination therapy with chemotherapy and anti-programmed cell death protein 1/programmed death-ligand 1 (anti-PD-1/PD-L1) therapy (chemo-immunotherapy). We previously observed that the increase of peripheral blood CD8+ T cells expressing CX3CR1, a marker of differentiation, correlates with response to anti-PD-1 therapy; however, the predictive and prognostic value of T-cell CX3CR1 expression during chemo-immunotherapy is unknown. Here, we evaluated the utility of circulating CX3CR1+CD8+ T cells as a predictive correlate of response to chemo-immunotherapy in patients with non-small cell lung cancer (NSCLC). At least 10% increase of the CX3CR1+ subset in circulating CD8+ T cells from baseline (CX3CR1 score) was associated with response to chemo-immunotherapy as early as 4 weeks with 85.7% overall accuracy of predicting response at 6 weeks. Furthermore, at least 10% increase of the CX3CR1 score correlated with substantially better progression-free (P = 0.0051) and overall survival (P = 0.0138) on Kaplan-Meier analysis. Combined single-cell RNA/T-cell receptor (TCR) sequencing of circulating T cells from longitudinally obtained blood samples and TCR sequencing of tumor tissue from the same patient who received a long-term benefit from the treatment demonstrated remarkable changes in genomic and transcriptomic signatures of T cells as well as evolution of TCR clonotypes in peripheral blood containing highly frequent tumor-infiltrating lymphocyte repertoires overexpressing CX3CR1 early after initiation of the treatment despite stable findings of the imaging study. Collectively, these findings highlight the potential utility of T-cell CX3CR1 expression as a dynamic blood-based biomarker during the early course of chemo-immunotherapy and a marker to identify frequent circulating tumor-infiltrating lymphocyte repertoires. Significance: Current approaches to combined chemotherapy and anti-PD-1/PD-L1 therapy (chemo-immunotherapy) for patients with NSCLC are limited by the lack of reliable predictive biomarkers. This study shows the utility of T-cell differentiation marker, CX3CR1, as an early on-treatment predictor of response and changes in genomic/transcriptomic signatures of circulating tumor-infiltrating lymphocyte repertoires in patients with NSCLC undergoing chemo-immunotherapy.

miR-210 has an antiapoptotic effect in pulmonary artery smooth muscle cells during hypoxia.

MicroRNAs (miRNAs) were recently reported to play an important role in the pathogenesis of pulmonary arterial hypertension (PAH), but it is not clear which miRNAs are important or what pathways are involved in the process. Because hypoxia is an important stimulus for human pulmonary artery smooth muscle cell (HPASMC) proliferation and PAH, we performed miRNA microarray assays in hypoxia-treated and control HPASMC. We found that miR-210 is the predominant miRNA induced by hypoxia in HPASMC. Induction of miR-210 was also observed in whole lungs of mice with chronic hypoxia-induced PAH. We found that transcriptional induction of miR-210 in HPASMC is hypoxia-inducible factor-1α dependent. Inhibition of miR-210 in HPASMC caused a significant decrease in cell number due to increased apoptosis. We found that miR-210 appears to mediate its antiapoptotic effects via the regulation of transcription factor E2F3, a direct target of miR-210. Our results have identified miR-210 as a hypoxia-inducible miRNA both in vitro and in vivo, which inhibits pulmonary vascular smooth muscle cell apoptosis in hypoxia by specifically repressing E2F3 expression.

Mycogenesis of gold nanoparticles using a phytopathogen Alternaria alternata.

The development of an eco-friendly and reliable process for the synthesis of gold nanomaterials (AuNPs) using microorganisms is gaining importance in the field of nanotechnology. In the present study, AuNPs have been synthesized by bio-reduction of chloroauric acid (HAuCl(4)) using the fungal culture filtrate (FCF) of Alternaria alternata. The synthesis of the AuNPs was monitored by UV-visible spectroscopy. The particles thereby obtained were characterized by UV, dynamic light scattering (DLS), X-ray diffraction (XRD), energy dispersive X-ray (EDX) analysis, Fourier transform infrared (FTIR) spectroscopy, atomic force microscopy (AFM) and transmission electron microscopy (TEM). Energy-dispersive X-ray study revealed the presence of gold in the nanoparticles. Fourier transform infrared spectroscopy confirmed the presence of a protein shell outside the nanoparticles which in turn also support their stabilization. Treatment of the fungal culture filtrate with aqueous Au(+) ions produced AuNPs with an average particle size of 12 ± 5 nm. This proposed mechanistic principal might serve as a set of design rule for the synthesis of nanostructures with desired architecture and can be amenable for the large scale commercial production and technical applications.