The use of neoadjuvant lobar radioembolization prior to major hepatic resection for malignancy results in a low rate of post hepatectomy liver failure

BackgroundNeoadjuvant yttrium-90 transarterial radioembolization (TARE) is increasingly being used as a strategy to facilitate resection of otherwise unresectable tumors due to its ability to generate both tumor response and remnant liver hypertrophy. Perioperative outcomes after the use of neoadjuvant lobar TARE remain underinvestigated.MethodsA single center retrospective review of patients who underwent lobar TARE prior to major hepatectomy for primary or metastatic liver cancer between 2007 and 2018 was conducted. Baseline demographics, radioembolization parameters, pre- and post-radioembolization volumetrics, intra-operative surgical data, adverse events, and post-operative outcomes were analyzed.ResultsTwenty-six patients underwent major hepatectomy after neoadjuvant lobar TARE. The mean age was 58.3 years (17–88 years). 62% of patients (n=16) had primary liver malignancies while the remainder had metastatic disease. Liver resection included right hepatectomy or trisegmentectomy, left or extended left hepatectomy, and sectorectomy/segmentectomy in 77% (n=20), 8% (n=2), and 15% (n=4) of patients, respectively. The mean length of stay was 8.3 days (range, 3–33 days) and there were no grade IV morbidities or 90-day mortalities. The incidence of post hepatectomy liver failure (PHLF) was 3.8% (n=1). The median time to progression after resection was 4.5 months (range, 3.3–10 months). Twenty-three percent (n=6) of patients had no recurrence. The median survival was 28.9 months (range, 16.9–46.8 months) from major hepatectomy and 37.6 months (range, 25.2–53.1 months) from TARE.ConclusionsMajor hepatectomy after neoadjuvant lobar radioembolization is safe with a low incidence of PHLF.     

Volume control associated with better cardiac function in long-term peritoneal dialysis patients.

BACKGROUND: This study was undertaken to investigate the effect of long-term blood pressure (BP) reduction, achieved with salt restriction and strict volume control, on frequency and regression of left ventricular hypertrophy (LVH) in long-term peritoneal dialysis (PD) patients. METHODS: 56 patients who had been treated for more than 2 years under our care were enrolled. After echocardiographic (Echo) evaluation, 46 patients were included in the follow-up study. In our unit, we aim to keep patients' BP below 130/85 mmHg and cardiothoracic index below 0.50. To reach these targets, moderate salt restriction is advised, and if necessary, hypertonic PD solutions are used. Echo was performed at the beginning of the study (after a mean period of 36 months on PD) and at the end of the prospective follow-up period (24 months later). RESULTS: At the time of the first Echo, LVH was detected in only 8 (21%) patients. Residual urine volume was significantly decreased compared to data taken when they first started PD (658 +/- 795 vs 236 +/- 307 mL/day). Mean left ventricular mass index (LVMI) was 107 +/- 26.5 g/m2. LVMI was significantly decreased at the end of the follow-up in patients who had LVH at baseline. No LVH developed in patients who had normal LVMI at baseline. CONCLUSION: Our results indicate that control of hypertension is possible when extracellular fluid volume is kept under control using hypertonic PD solutions in case of recruitment in addition to salt restriction in long-term PD patients. Sustained normovolemia is associated with low incidence and regression of LVH.     

Nuclear p53 Overexpression in Bladder, Prostate, and Renal Carcinomas

Background :
The aim of this study was to examine nuclear p53 overexpression in transitional cell carcinoma of the bladder, adenocarcinoma of the prostate, and renal cell carcinoma.
Methods :
Forty-four pathologic specimens from 39 bladder cancer patients, 41 prostatic adenocarcinoma, and 39 renal cell carcinoma specimens were analyzed immunohistochemically with D07 monoclonal antibody to detect the expression of the mutant p53 gene. Overexpression was said to occur when the number of positively-stained tumor nuclei were≥ 10% in each specimen. p53 overexpression was correlated with the clinical and histopathological features of these cancers.
Results :
Nuclear p53 overexpression occurred in 18.2% of transitional cell bladder cancer specimens, 12.2% of prostate cancer specimens, and 17.9% of renal cell cancer specimens. Statistical analyses showed that grade, vascular invasion, and necrosis in bladder cancer, a high Gleason score in prostate cancer, and the 1-year mortality rate in renal cancer were significantly related with p53 nuclear overexpression (P<0.05).
Conclusion :
Using the D07 monoclonal antibody, nuclear p53 overexpression is relatively uncommon in urologic malignancies, and moderately correlates with several histopathological and clinical features of urologic malignancies.     

Effective high-capacity gutless adenoviral vectors mediate transgene expression in human glioma cells.

Glioblastoma multiforme (GBM) is the most common subtype of primary malignant brain tumor. Although serotype 5 adenoviral vectors (Ads) have been used successfully in clinical trials for GBM, the capacity of Ads to infect human glioma cells and the expression of adenoviral receptors in GBM cells have been challenged. In this report, we studied the expression of three molecules that have been shown to mediate adenoviral entry into cells, i.e., coxsackie and adenovirus receptor (CAR), integrin alphavbeta3 (INT), and major histocompatibility complex class I (MHCI), in rodent glioma cell lines and low-passage primary cultures and cell lines from human GBM. We correlated levels of expression of CAR, INT, and MHCI with transduction efficiency elicited by several high-capacity helper-dependent adenoviral vectors (HC-Ads). Expression levels of adenoviral receptors were variable among the different GBM cells studied. HC-Ad-mediated therapeutic gene expression was efficient, ranging between 20 and 80% of the total target cells expressing the encoded transgenes. Our results show no correlation between the levels of CAR, INT, or MHCI molecules and the levels of transgene expression or the number of GBM cells transduced. We conclude that expression levels of adenoviral receptors do not predict their transduction efficiency or biological function.     

Defective Acidification in Human Breast Tumor Cells and Implications for Chemotherapy

Multidrug resistance (MDR) is a significant problem in the treatment of cancer. Chemotherapeutic drugs distribute through the cyto- and nucleoplasm of drug-sensitive cells but are excluded from the nucleus in drug-resistant cells, concentrating in cytoplasmic organelles. Weak base chemotherapeutic drugs (e.g., anthracyclines and vinca alkaloids) should concentrate in acidic organelles. This report presents a quantification of the pH for identified compartments of the MCF-7 human breast tumor cell line and demonstrates that (a) the chemotherapeutic Adriamycin concentrates in acidified organelles of drug-resistant but not drug-sensitive cells; (b) the lysosomes and recycling endosomes are not acidified in drug-sensitive cells; (c) the cytosol of drug-sensitive cells is 0.4 pH units more acidic than the cytosol of resistant cells; and (d) disrupting the acidification of the organelles of resistant cells with monensin, bafilomycin A1, or concanamycin A is sufficient to change the Adriamycin distribution to that found in drug-sensitive cells, rendering the cell vulnerable once again to chemotherapy. These results suggest that acidification of organelles is causally related to drug resistance and is consistent with the hypothesis that sequestration of drugs in acidic organelles and subsequent extrusion from the cell through the secretory pathways contribute to chemotherapeutic resistance.     

Using diazepam and atropine before strabismus surgery to prevent postoperative nausea and vomiting: a randomized, controlled study.

OBJECTIVE: To evaluate the efficacy of diazepam and atropine sulfate premedication in preventing nausea and vomiting after strabismus surgery under general anesthesia. METHODS: Fifty children age 4 to 15 years who underwent strabismus surgery at Cukurova University Medical Faculty, Department of Ophthalmology, from February 2000 to June 2000 were randomized into 2 groups: 25 children in the control group did not receive premedication, whereas 25 children in the treatment group received premedication with 0.15 mg/kg diazepam and 0.015 mg/kg atropine sulfate. Occurrence of postoperative nausea and vomiting (PONV) was recorded. RESULTS: The incidence of PONV was lower in the premedicated group (P <.018, chi(2) test). CONCLUSIONS: It is concluded that diazepam and atropine sulfate premedication decreases nausea and vomiting after strabismus surgery.     

A clinico-pathological study of laryngeal and hypopharyngeal carcinoma: correlation of cord-arytenoid mobility with histopathologic involvement.

OBJECTIVE: This study evaluates the vocal cord and arytenoid mobility in relation to the tumoral involvement of the cricoarytenoid joint (CAJ), thyroarytenoid (TA) muscle, and posterior cricoarytenoid (PCA) muscle in whole-organ sections of total laryngectomy specimens. STUDY DESIGN AND SETTING: The study was prospectively carried out between 1998 and 2003 and involved 133 primary squamous cell carcinoma cases of larynx or pyriform sinus that were treated with total laryngectomy. Preoperative mobility of vocal cords and arytenoids were evaluated separately and correlated with histopathologic findings. RESULTS: In cases with fixed vocal cord CAJ, TA muscle, and PCA muscle were involved in 42.4%, 72.9%, and 27.1% of the cases, respectively, while in cases with fixed arytenoid these structures were affected in 40%, 66.3%, and 25.3% of the cases. Weight effect seemed to play a role in 60% and 50% of the cases of supraglottic and pyriform sinus carcinoma, respectively. CONCLUSION: Careful evaluation of the mobility of the cord arytenoid unit separately helps the surgeon to better understand the patterns of tumoral extension guiding for the appropriate surgery which should be undertaken.     

Inhibition of chemokines prevents intraperitoneal adhesions in mice

BACKGROUND: The present study evaluates the efficacy of a broad-spectrumchemokine inhibitor, NR58-3.14.3, in the prevention of adhesionformation after i.p. surgery in mice. METHODS: A total of 110eight week old female Balb/c mice underwent laparotomy. Fortyanimals were randomly assigned to receive daily i.p. injectionsof either vehicle (control) or NR58-3.14.3. Time-course of adhesionformation was assessed. A titration of NR58-3.14.3 was conductedfor i.p. and s.c. administrations. The effectiveness of a singleintra-operative dose of NR58-3.14.3 was evaluated. Number, extent,location and type of adhesions were recorded. Immunohistochemistryof adhesions was done with leukocyte common antigen, CD45. RESULTS:Adhesion scores peaked on post-operative days 6–8. Onboth days 6 and 8, there were smaller adhesion size and lowercumulative adhesion scores in NR58-3.14.3-treated group. Moreover,on day 8, there were significantly fewer adhesions in NR58-3.14.3-treatedgroup compared to controls. The least effective dose for i.p.administration of NR58-3.14.3 was 0.45 mg/animal. Subcutaneousand single intra-operative i.p. administrations were also effectivein the prevention of i.p. adhesions. Although NR58-3.14.3 decreasedthe number of CD45⁺ inflammatory cells in the adhesions by 22.5%compared to control group, this was not significant. CONCLUSIONS:Our results show that this broad-spectrum chemokine inhibitorprevents post-operative adhesions in mice and may have a potentialclinical use.