Neutrophil to Lymphocyte Ratio in Patients Who Received Neoadjuvant Treatment before Gastrectomy.

BACKGROUND: The neutrophil to lymphocyte ratio (NLR) has demonstrated prognostic value in various malignant conditions, including gastric adenocarcinoma. However, chemotherapy may affect NLR. OBJECTIVES: To evaluate the prognostic value of NLR as an accessory decision-making tool in terms of operating patients after neoadjuvant chemotherapy in patients with resectable gastric cancer. METHODS: We collected oncologic, perioperative, and survival data of patients with gastric adenocarcinoma who underwent curative intent gastrectomy and D2 lymphadenectomy between 2009 and 2016. The NLR was calculated from preoperative laboratory tests and classified as high (> 4) and low (≤ 4). The t-test, chi-square, Kaplan-Meier analysis, and Cox multivariate regression models were used to assess associations of clinical, histologic, and hematological variables with survival. RESULTS: For 124 patients the median follow-up was 23 months (range 1-88). High NLR was associated with greater rate of local complication (r=0.268, P < 0.01). The rate of major complications (Clavien-Dindo ≥ 3) was higher in the high NLR group (28% vs. 9%, P = 0.022). Among the 53 patients who received neoadjuvant chemotherapy, those with low NLR had significantly improved disease-free survival (DFS) (49.7 vs. 27.7 months, P = 0.025). Low NLR was not significantly associated with overall survival (mean survival, 51.2 vs. 42.3 months, P = 0.19). Multivariate regression identified NLR group (P = 0.013), male gender (P = 0.04), and body mass index (P = 0.026) as independently associated with DFS. CONCLUSIONS: Among gastric cancer patients planned for curative intent surgery who underwent neoadjuvant chemotherapy, NLR may have prognostic value, particularly regarding DFS and postoperative complications.

Flange Fracture and Dislocation: An Unusual Complication of Percutaneous Tracheostomy.

Percutaneous dilational tracheostomy (PDT) is a commonly used technique in intensive care units (ICUs) for persistent respiratory failure. Early complications of placement includeairway loss, bleeding, and tracheal ring fracture. Tracheostomy tube fracture is a rarely reported complication that can lead to loss of airway and require emergent intervention. We present two case reports of tracheostomy flange fracture and dislocation after PDT. Shortly after insertion, the tracheostomy flange was incidentally noted to have irreparably fractured and separated from the outer cannula. Both patients were orotracheally intubated and converted to open revisional surgical tracheostomy. Outer cannula separation from the flange is a rare but important complication of PDT due to the risk of occult airway loss. The tracheostomy tube supplied in the PDT set is manufactured in three parts and the plastic outer cannula is snapped to the silicone flange during manufacturing. The flange is not meant to be separated during insertion or use. PDT insertion requires significant force to be exerted, as the catheter has to travel through the subcutaneous tissue of the neck before entering the trachea. These cases suggest that the junction of the flange and the outer cannula may be a weak point and that fracture and dislocation at that site may occur due to excessive or misdirected force. Dislocation may cause loss of airway and a need for orotracheal intubation as performed in our cases. Understanding this complication and carefully examining the flange after placement is essential for early recognition to avoid loss of airway.

[THE EFFECTS OF HORMONAL REPLACEMENT THERAPY (HRT) ON MAMMOGRAPHIC BREAST DENSITY AND ABNORMAL MAMMOGRAMS PROMPTING FURTHER INVESTIGATION].

AIMS: The purpose of this study was to portray and analyze the inter-relationship between the use of HRT, mammographic breast density and the finding of any mammographic abnormality that prompted further investigation such as core needle biopsy or additional imaging testing, while controlling for obstetric and relevant demographic data. BACKGROUND: Mammographic breast density has been associated with higher risk of breast cancer and decrease in its sensitivity, while hormonal replacement therapy (HRT) in turn, has been implicated in increasing mammographic density and is considered a risk factor for breast cancer by itself. The inter-relationship between HRT, breast density and any mammographic or sonographic finding requiring further investigation has not been fully investigated. METHODS: A total of 2,758 consecutive, screening mammograms performed during one year in a single academic medical center in Israel were analyzed. Each mammogram was supplemented by high resolution ultrasound. Density was measured by a visual, semi-quantitative, 5-grade scale, based on Boyd's classification and grouped into low density mammograms (LDM) (1-3) and high density mammograms (HDM) (4-5). Demographic and obstetric data, personal and family history of breast cancer, and the use of HRT were entered into the database. These parameters were correlated with breast density and any detected abnormality that prompted further investigation. Univariate and multivariate analyses as well as multivariate logistic regression were performed using SAS 9.2. RESULTS: A significant difference in density was observed between pre- and post-menopausal women (p = 0.0001). However, the use of HRT in post-menopausal women was not associated with higher incidence of HDM (18.6%, n=110/592) compared to post-menopausal women without HRT (15.4%, n=211/1370) (p=n.s). Mammographic abnormality was more likely to occur in post-menopausal women without HRT (52%, n=711/1370) compared with women on HRT (38.7% n=229/592) (p = 0.0001). This held true for solid lump (p=0.0001), tissue irregularity (p=0.016) and calcifications (p=0.0005). Menopause was associated with higher likelihood (48%) of any mammographic finding compared with 41.6% in pre-menopausal women (p = 0.0017). A total of 266 women with mammographic findings prompting histological assessment were identified, revealing 105 malignant lesions. HRT in post-menopausal women was associated with lower incidence (28%) of malignancy compared to post-menopausal women without HRT (50%). CONCLUSIONS: The present study, portraying the inter-relationship between mammographic breast density, any abnormal finding in screening mammograms, and the use of HRT has not found such treatment to be associated neither with increased density, nor with higher probability of finding malignancy. Furthermore, a lower incidence of mammographic abnormality was noted in HRT users. Albeit, further and larger studies are required to substantiate these findings. The results of this study do not support the notion that HRT increases the likelihood of malignancy or affects breast density.

Risk Factors for Complications of Total/Subtotal Gastrectomy for Gastric Cancer: Prospectively Collected, Based on the Clavien-Dindo Classification System.

BACKGROUND: Recent studies have analyzed risk factors associated with complications after gastric cancer surgery using the Clavien-Dindo classification (CD). However, they have been based on Asian population cohorts (Chinese, Japanese, Korean). OBJECTIVES: To prospectively analyze all post-gastrectomy complications according to severity using CD classification and identify postoperative risk factors and complications. METHODS: We analyzed all gastrectomies for gastric cancer performed 2009-2014. Recorded parameters included demographic data, existing co-morbidities, neo-adjuvant treatment, intra-operative findings, postoperative course, and histologic findings. Postoperative complications were graded using CD classification. RESULTS: The study comprised 112 patients who underwent gastrectomy. Mean age was 64.8 ± 12.8 years; 53 patients (47%) underwent gastrectomy, 37 (34%) total gastrectomy, and 22 (19%) total extended gastrectomy. All patients had D2 lymphadenectomy. The average number of retrieved lymph nodes was 35 ± 17. Severe complication rate (≥ IIIa) was 14% and mortality rate was 1.8%. In a univariate analysis, age > 65 years; ASA 3 or higher; chronic renal failure; multi-organ resection; and tumor, node, and metastases (TNM) stage ≥ IIIc were found to be significantly associated with CD complication grade > III (P = 0.01, P = 0.05, P = 0.04, P = 0.04, and P = 0.01, respectively). Multivariate regression analysis revealed advanced stage (≥ IIIc) and age > 65 years to be significant independent risk factors (P < 0.05). CONCLUSIONS: Age > 65 and advanced stage (≥ IIIc) were the primary risk factors for complications of grade > III according to the CD classification following gastrectomy for gastric cancer.

CHOP is a critical regulator of acetaminophen-induced hepatotoxicity.

BACKGROUND & AIMS: The liver is a major site of drug metabolism and elimination and as such is susceptible to drug toxicity. Drug induced liver injury is a leading cause of acute liver injury, of which acetaminophen (APAP) is the most frequent causative agent. APAP toxicity is initiated by its toxic metabolite NAPQI. However, downstream mechanisms underlying APAP induced cell death are still unclear. Endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) have recently emerged as major regulators of metabolic homeostasis. UPR regulation of the transcription repressor CHOP promotes cell death. We analyzed the role of UPR and CHOP in mediating APAP hepatotoxicity. METHODS: A toxic dose of APAP was orally administered to wild type (wt) and CHOP knockout (KO) mice and damage mechanisms were assessed. RESULTS: CHOP KO mice were protected from APAP induced damage and exhibited decreased liver necrosis and increased survival. APAP metabolism in CHOP KO mice was undisturbed and glutathione was depleted at similar kinetics to wt. ER stress and UPR activation were overtly seen 12h following APAP administration, a time that coincided with strong upregulation of CHOP. Remarkably, CHOP KO but not wt mice exhibited hepatocyte proliferation at sites of necrosis. In vitro, large T immortalized CHOP KO hepatocytes were protected from APAP toxicity in comparison to wt control cells. CONCLUSIONS: CHOP upregulation during APAP induced liver injury compromises hepatocyte survival in various mechanisms, in part by curtailing the regeneration phase following liver damage. Thus, CHOP plays a pro-damage role in response to APAP intoxication.