Comparison of clinical utility between neutrophil count and neutrophil–lymphocyte ratio in patients with ovarian cancer: a single institutional experience and a literature review

Objective

We retrospectively investigated the prognostic significance and clinical utility of pretreatment neutrophilia and elevated neutrophil–lymphocyte ratio (NLR) in patients with epithelial ovarian cancer.

Methods

Clinical data were collected from 344 surgically staged ovarian cancer patients between April 2007 and March 2016 and retrospectively reviewed. Neutrophilia and elevated NLR were defined as a neutrophil count ≥ 8,000/μl and an NLR ≥ 4.0, respectively. Univariate or multivariate analysis was conducted to evaluate the association between pretreatment neutrophilia or elevated NLR and clinicopathological characteristics, optimal surgery rate, progression-free survival (PFS) and disease-specific survival (DSS). Finally, we compared the clinical utility between neutrophil count and NLR by receiver operating characteristic (ROC) analysis.

Results

Pretreatment neutrophilia and elevated NLR were observed in 24 (7.0%) and 142 (41.3%) patients, respectively. In univariate analysis, both neutrophilia and elevated NLR were found to be associated with short PFS and DSS (p < 0.005). Multivariate analysis showed that neutrophilia and elevated NLR were predictors for shorter survival. In ROC analysis, the NLR tended to have a greater area under the ROC curve (AUC) value than the neutrophil count in predicting recurrence (0.7011 vs 0.6516, p = 0.0546) and had a significantly greater AUC value in predicting DSS (0.7249 vs 0.6379, p = 0.0182). Finally, based on the neutrophil count and NLR, we divided the patients into 3 prognostic groups—high-risk group (elevated NLR with neutrophilia), intermediate-risk group (elevated NLR without neutrophilia), and low-risk group (normal NLR), which allows for individualized and accurate survival estimates.

Conclusions

Pretreatment neutrophilia and elevated NLR are independent poor prognostic factors in epithelial ovarian cancer patients. The NLR was superior to neutrophil count in predicting the survival of epithelial ovarian cancer patients.

     

Prostate-specific membrane antigen in breast cancer: a comprehensive evaluation of expression and a case report of radionuclide therapy

Purpose

Prostate-specific membrane antigen (PSMA), a protein product of the folate hydrolase 1 (FOLH1) gene, is gaining increasing acceptance as a target for positron emission tomography/computer tomography (PET/CT) imaging in patients with several cancer types, including breast cancer. So far, PSMA expression in breast cancer endothelia has not been sufficiently characterized.

Methods

This study comprised 315 cases of invasive carcinoma of no special type (NST) and lobular breast cancer (median follow-up time 9.0 years). PSMA expression on tumor endothelia was detected by immunohistochemistry. Further, vascular mRNA expression of the FOLH1 gene (PSMA) was investigated in a cohort of patients with invasive breast cancer provided by The Cancer Genome Atlas (TCGA).

Results

Sixty percent of breast cancer cases exhibited PSMA-positive endothelia with higher expression rates in tumors of higher grade, NST subtype with Her2-positivity, and lack of hormone receptors. These findings were confirmed on mRNA expression levels. The highest PSMA rates were observed in triple-negative carcinomas (4.5 × higher than in other tumors). Further, a case of a patient with metastatic breast cancer showing PSMA expression in PET/CT imaging and undergoing PSMA radionuclide therapy is discussed in detail.

Conclusions

This study provides a rationale for the further development of PSMA-targeted imaging in breast cancer, especially in triple-negative tumors.

     

lmmuno Histochemical Profile of Endometrium in Patients With Genital Endometriosis

The aim of present study was to investigate the occurence of different lymphocyte subsets in the endometrium of endometriosis patients and in healthy women on every day of the menstrual cycle with special emphasis to the proliferative activity of endometrial cells with Ki-S3 antibody. We also conducted immunohistochemical studies of T-lymphocytes, B-lympho-cytes, macrophages, natural-killer-cells and also of antigens class II of the histocompatibility complex (HLA-DR) during the different phases of the menstrual cycle in endometriosis and non-endometriosis patients.Endometrial lymphocyte subsets show equal quantity and distribution in endometriosis patients and in the control group. After a peak in the early preoliferative phase the absolute number of T-lymphocytes decreases while a predominance of T-suppressor/cytotoxic T-lymphocytes (CD8) compared to T-helper/inducer lymphocytes (CD4) occurs towards the end of the menstrual cycle.It can be concluded that endometrium as the potential parent epithelia of endometriotic lesions seems not to be altered in its lymphatic cell content compared to healthy women. Furthermore endometrium is clearly characterised as part of the mucosa associated lymphatic tissue (MALT). T-lymphocytes show specific quantitative changes due to different phases of the menstrual cycle.     

Platelets enhance contractility in perfused rat mesenteric arteries: Involvement of endothelin-1

We investigated the effects of platelet supernatant on pressor responses to norepinephrine in isolated perfused rat mesenteric arteries. Perfusion of the arteries with platelet supernatant for 2 h markedly enhanced the pressor responses to norepinephrine (10⁻⁶ and 3×10⁻⁶ M). This enhancement was significantly inhibited by phosphoramidon (10⁻⁴ M), an endothelin converting enzyme inhibitor. Both BQ788 [N-cis-2,6-dimethylpiperidinocarbonyl-

Full-size image

-γ-methylleucyl-

Full-size image

-1-methoxycarbonyltryptophanyl-

Full-size image

-norleucine] (10⁻⁶ M), an endothelin ET_B receptor antagonist, and bosentan (Ro47-0203, 4-tert-butyl-N-[6-(2-hydroxy-ethoxy)-5-(2-methoxy-phenoxy)-2,2´-bipyrimidin-4-yl]-benzenesulfonamide) (10⁻⁵ M), a nonselective endothelin receptor antagonist, also prevented the potentiation of responses to norepinephrine evoked by platelet supernatant, but FR139317 ((R)2-[(R)-2-[(S)-2-[[1-(hexahydro-1H-azepinyl)]carbonyl]amino-4-methyl-pentanoyl] amino-3-[3-(1-methyl-1H-indoyl)]propionyl]amino-3-(2-pyridyl) propionic acid) (10⁻⁶ M), an endothelin ET_A receptor antagonist, had little effect. Suppressor doses of endothelin-1 (3×10⁻¹⁰ M) or sarafotoxin S6c (S6c) (3×10⁻¹⁰ M) potentiated significantly the norepinephrine-induced vasoconstriction, in the same preparation. Moreover, supernatant-induced enhancement of pressor responses to norepinephrine was markedly suppressed by TGF-β1 neutralizing antibody. Transforming growth factor-β1 (TGF-β1) (40 pM) also significantly enhanced the pressor responses to norepinephrine (10⁻⁶ M) and this enhancement was significantly inhibited by phosphoramidon. These results suggest that platelet-derived TGF-β1 stimulates the vascular production of endothelin-1 and thereby enhances vasoconstrictor responses to norepinephrine. Platelet-induced enhancement of vasoconstrictor responses to norepinephrine seems to be mainly mediated by endothelin ET_B receptor, in rat mesenteric arteries.     

Is old age a contraindication to elective ventral hernia repair?

Background

Ventral hernia repair (VHR) is a frequent problem in the expanding aging population. However, advanced age is often viewed as a contraindication to elective hernia surgery. We aimed to analyze outcomes of VHR in a large cohort of elderly patients. We hypothesized that elective VHR is safe and effective even in patients over 70 years old.

Methods

We conducted a retrospective review of consecutive patients over the age of 70 who underwent VHR at a at a tertiary care hospital. Main outcome measures included postoperative complications and recurrence rate.

Results

Between 2006 and 2015, 263 elderly patients who underwent elective VHR were included. Major comorbidities included diabetes, COPD, and smoking history. The majority of the patients underwent open repairs. Surgical site events occurred in 54 patients (21%). Postoperative complications included 17 venous thromboembolism occurrences, 2 myocardial infarctions, 41 patients who required postoperative critical care, and 1 mortality. Readmission within 90 days postoperatively occurred in 34 patients (13%). At a mean follow-up of 25.6 months, 17 patients in the open group and 6 patients in the laparoscopic group had a recurrence.

Conclusion

We demonstrated that VHR can be performed reasonably safely and effectively even in this potentially risky cohort. The use of laparoscopy might be associated with further reduction in morbidity. Overall, age should not be a contraindication to elective VHR, even in patients over 70 years old.

     

Preparation of chondroitin sulfate-adipic acid dihydrazide-doxorubicin conjugate and its antitumour characteristics against LLC cells

Macromolecule–antitumour drug conjugates can reach tumour sites specifically via the enhanced permeability and retention (EPR) effect. It is desirable to release the drug efficiently from the conjugate at acidic pH in the tumour tissue or in the endosomes of cancer cells. In this study, we attempted to produce a carrier system with a labile chemical bond at acidic pH. Adipic acid dihydrazide (ADH)-chondroitin sulfate (CS) (termed CS-ACH) was synthesised by a two-step method, with the introduction of formyl groups followed by reductive amination using ADH. Doxorubicin (DOX) was conjugated to CS-ACH by simple mixing at acidic pH. The conjugate, designated CS-ACH-DOX, showed gradual drug release pH dependently at 37?°C; after incubation for seven days, more than 60% of DOX was released at pH 4, whereas less than 20% was released at pH 7. CS-ACH-DOX showed in vitro cytotoxicity against Lewis lung carcinoma (LLC) cells, which was less effective than that of DOX itself. However, CS-ACH-DOX inhibited tumour growth more than DOX in LLC tumour-bearing mice. These results suggested that CS-ACH-DOX might accumulate in tumours via the EPR effect and release DOX effectively at acidic pH. CS-ACH-DOX was considered to act as a drug delivery system with tumour targeting.     

A Study of Moisture Sorption and Dielectric Processes of Starch and Sodium Starch Glycolate

Purpose

This study explored the potential of combining the use of moisture sorption isotherms and dielectric relaxation profiles of starch and sodium starch glycolate (SSG) to probe the location of moisture in dried and hydrated samples.

Methods

Starch and SSG samples, dried and hydrated, were prepared. For hydrated samples, their moisture contents were determined. The samples were probed by dielectric spectroscopy using a frequency band of 0.1 Hz to 1 MHz to investigate their moisture-related relaxation profiles. The moisture sorption and desorption isotherms of starch and SSG were generated using a vapor sorption analyzer, and modeled using the Guggenheim-Anderson-de Boer equation.

Results

A clear high frequency relaxation process was detected in both dried and hydrated starches, while for dried starch, an additional slower low frequency process was also detected. The high frequency relaxation processes in hydrated and dried starches were assigned to the coupled starch-hydrated water relaxation. The low frequency relaxation in dried starch was attributed to the local chain motions of the starch backbone. No relaxation process associated with water was detected in both hydrated and dried SSG within the frequency and temperature range used in this study. The moisture sorption isotherms of SSG suggest the presence of high energy free water, which could have masked the relaxation process of the bound water during dielectric measurements.

Conclusion

The combined study of moisture sorption isotherms and dielectric spectroscopy was shown to be beneficial and complementary in probing the effects of moisture on the relaxation processes of starch and SSG.

     

Bilateral pallidotomy for Meige syndrome

Meige syndrome (MS) is usually described as a combination of blepharospasm with oromandibular dystonia. There are a large number of case reports of deep brain stimulation (DBS) of the globus pallidus internus (GPI) for MS and only one report of unilateral pallidotomy (PT). We report the first case of staged bilateral PT for treatment of a patient with MS using intraoperative high-frequency stimulation in order to predict and prevent postoperative deficit. There was a significant improvement of the Burk-Fahn-Marsden dystonia rating scale from 26 to 3. There were no adverse postoperative neurological and neuropsychological events.