Translational studies suggest that excess perioperative release of catecholamines and prostaglandins may facilitate metastasis and reduce disease-free survival. This trial tested the combined ...perioperative blockade of these pathways in breast cancer patients.
In a randomized placebo-controlled biomarker trial, 38 early-stage breast cancer patients received 11 days of perioperative treatment with a β-adrenergic antagonist (propranolol) and a COX-2 inhibitor (etodolac), beginning 5 days before surgery. Excised tumors and sequential blood samples were assessed for prometastatic biomarkers.
Drugs were well tolerated with adverse event rates comparable with placebo. Transcriptome profiling of the primary tumor tested
hypotheses and indicated that drug treatment significantly (i) decreased epithelial-to-mesenchymal transition, (ii) reduced activity of prometastatic/proinflammatory transcription factors (GATA-1, GATA-2, early-growth-response-3/EGR3, signal transducer and activator of transcription-3/STAT-3), and (iii) decreased tumor-infiltrating monocytes while increasing tumor-infiltrating B cells. Drug treatment also significantly abrogated presurgical increases in serum IL6 and C-reactive protein levels, abrogated perioperative declines in stimulated IL12 and IFNγ production, abrogated postoperative mobilization of CD16
"classical" monocytes, and enhanced expression of CD11a on circulating natural killer cells.
Perioperative inhibition of COX-2 and β-adrenergic signaling provides a safe and effective strategy for inhibiting multiple cellular and molecular pathways related to metastasis and disease recurrence in early-stage breast cancer.
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The purpose of this study was to assess pathological complete response and whether it serves a surrogate for survival among patients receiving neo-adjuvant doxorubicin–cyclophosphamide followed by ...paclitaxel for triple-negative breast cancer with respect to
BRCA1
mutation status. From a neo-adjuvant systemic therapy database of 588 breast cancer cases, 80 triple-negative cases who had undergone BRCA genotyping were identified. Logistic regression model was fitted to examine the association between
BRCA1
status and pathological complete response. Survival outcomes were evaluated using Kaplan–Meier method, differences between study groups calculated by log-rank test. Thirty-four
BRCA1
carriers and 43 non-carriers were identified. The
BRCA1
carriers had pathological complete response rate of 68 % compared with 37 % among non-carriers,
p
= 0.01. Yet this did not translate into superior survival for
BRCA1
carriers compared with non-carriers. No difference in relapse-free survival were noted among those with or without pathological complete response in
BRCA1
carriers regardless of pathological complete response status (Log-rank
p
= 0.25), whereas in the non-carrier cohort, relapse-free survival was superior for those achieving pathological complete response (Log-rank
p
< 0.0001). Response to neo-adjuvant systemic therapy differed in
BRCA1
-associated triple-negative breast cancer compared with triple-negative non-carriers, with a higher rate of pathological complete response. However, compared with non-carrier triple-negative breast cancer, pathological complete response was not a surrogate for superior relapse-free survival in
BRCA1
patients. Future studies using specific chemotherapy regimens may provide further improvements in outcomes.
Background
The traditional open approach to incarcerated inguinal hernia has several drawbacks including difficulty avoiding tension in the swollen and edematous tissues leading to a higher ...recurrence rate, possible contamination of the mesh if it is implanted in an area of bowel strangulation, and proper evaluation of whether ischemic bowel requires resection or not, which may mandate laparotomy. This study aimed to evaluate an approach that combines intraperitoneal laparoscopic exploration with hernia reduction and total extraperitoneal (TEP) repair of the hernia.
Methods
An exploratory laparoscopy is performed. The incarcerated content is gently retracted into the abdominal cavity and inspected. If no resection is needed, the gas is deflated, the umbilical trocar is removed, and the preperitoneal space is accessed with a Hasson trocar inserted behind the rectus muscle toward the pelvis. Two additional 5-mm trocars are inserted into the preperitoneal space in the lower midline. A standard TEP repair with mesh is performed.
Results
Between 2005 and 2008, 15 patients underwent laparoscopic exploration for incarcerated inguinal hernia followed by TEP repair. Of the 15 patients, 8 had acute incarceration and 7 had chronic irreducible hernia. Reduction of the incarcerated content was straightforward, and no bowel resection was needed. No major complications or wound or mesh infections occurred.
Conclusion
The combined laparoscopic approach offers a solution to incarceration of inguinal hernias while taking advantage of each separate approach. The first part of the procedure enables easy reduction of the incarcerated content and assessment of its viability. The second part enables a simple and standard repair, similar to that for an elective case. If bowel necrosis is suspected preoperatively, an open anterior approach should be taken to avoid possible intraabdominal contamination.
Factor VII deficiency is the most common among the rare autosomal recessive coagulation disorders worldwide. In factor VII deficient patients, the severity and clinical manifestations cannot be ...reliably determined by factor VII levels. Severe bleeding tends to occur in individuals with factor VII activity levels of 2% or less of normal. Patients with 2-10% factor VII vary between asymptomatic to severe life threatening haemorrhages behaviour. Recombinant factor VIIa (rFVIIa) is the most common replacement therapy for congenital factor VII deficiency. However, unlike haemophilia patients for whom treatment protocols are straight forward, in asymptomatic factor VII deficiency patients it is still debatable. In this study, we demonstrate that a single and very low dose of recombinant factor VIIa enabled asymptomatic patients with factor VII deficiency to go through major surgery safely. This suggestion was also supported by thrombin generation, as well as by thromboelastometry.
Mechanical bowel preparation prior to colorectal surgery may reduce infectious complications, facilitate tumor localization, and allow intraoperative colonoscopy, if required. However, recent data ...suggest that mechanical bowel preparation may not facilitate a reduction in infectious complications. During laparoscopic colectomy, manual palpation is blunt, thereby potentially compromising tumor localization. The aim of this study was to assess the utility of mechanical bowel preparation in laparoscopic colectomy.
A retrospective medical record review of all patients who underwent laparoscopic colectomy was performed. Patients were divided into two groups: those who had preoperative mechanical bowel preparation (Group A) or those who did not (Group B). All relevant perioperative data were reviewed and compared.
Two hundred patients underwent laparoscopic colectomy; 68 (34%) were in Group A and 132 (66%) were in Group B. Sixteen (8%) patients required intraoperative colonoscopy for localization and were evenly distributed between the two groups. The incidence of conversion to laparotomy was slightly higher in Group B (14 vs 9%) due to difficult localization in some cases; however, this difference did not reach statistical significance. Furthermore, there was no significant difference in the postoperative complication rate between the two groups. Specifically, an anastomotic leak and a wound infection were recorded in 4 and 12% of patients in Group A compared to 3 and 17% in Group B, respectively.
Laparoscopic colectomy may be safely performed without preoperative mechanical bowel preparation, although difficult localization may lead to a slightly higher conversion rate. Appropriate patient selection for laparoscopic colectomy without mechanical bowel preparation is essential. Furthermore, bowel preparation should be considered in cases of small and nonpalpable lesions.
Background
Acute appendicitis (AA) is a common indication for urgent abdominal surgery. CA‐125 glycoprotein antigen is a non‐specific marker for epithelial ovarian cancer; CA‐125 serum levels also ...increased in the conditions of peritoneal inflammation. The aim of this study was to examine the correlation between serum CA‐125 levels and AA.
Methods
All emergency department (ED) patients with suspected AA were prospectively enrolled in the study. The serum level of CA‐125 was checked in every patient on arrival to the ED in addition to the routine clinical and laboratory evaluation. Data regarding demographic, clinical, radiological, operative and pathological features were analysed.
Results
One hundred consecutive patients (48 males) were enrolled in the study. We found a statistically significant correlation between CA‐125 levels in males and the severity of appendicitis as described in the operative and pathology reports (P = 0.008 and P = 0.02, respectively). In addition, we observed a trend towards higher levels of CA‐125 in males with AA compared with males without AA (9.9 ± 4.7 versus 7.8 ± 3.2 U/mL, respectively; P = 0.09).
Conclusions
CA‐125 levels correlate with the severity of appendicitis in males and may serve as a surrogate marker for the severity of other intra‐abdominal surgical diseases.
Male breast cancer (MBC) is a rare disease that is poorly understood. Treatment protocols are widely extrapolated from breast cancer in women.
To review the experience with MBC of a single center in ...Israel over a period of 22 years.
This single center retrospective study evaluated all patients diagnosed with MBC over a period of 22 years (1993-2015). Data were extracted from patient medical charts and included demographics, clinical, surgical, and oncological outcomes.
The study comprised 49 patients. Mean age at diagnosis was 64.1 ± 13.5 years. The majority were diagnosed at early stages (1A-2A) (54.4%), 30.6% were stage 3B mostly due to direct skin and nipple involvement, and 59.2% of the patients had node negative disease. All of the patients were diagnosed with invasive ductal carcinoma and 30.6% had concomitant ductal carcinoma in situ. Estrogen receptor (ER) status was predominantly positive and luminal B (HER2-) was the most common subtype. Of the patients, 18.4% were BRCA carriers. The majority of patients underwent mastectomy. Radiotherapy was delivered to 46.9% and hormonal therapy to 89.8%. Chemotherapy was administered to 42.9%. Overall survival was 79.6% with a median survival of 60.1 (2-178) months; 5- and 10-year survival was 93.9% and 79.6%, respectively. Progesterone receptor (PR)-negative patients had a significantly improved overall survival.
MBC has increasing incidence. PR-negative status was associated with better overall survival and disease-free interval. Indications to radiotherapy and hormonal therapy need standardization and will benefit from prospective randomized control trials.
Technical information for handling fine-needle aspiration samples from thyroid lesions for WETSEM electron microscopy is presented. The use of wet SEM technology maintains cytological features of the ...thyroid cells, in the atmospheric electronic microscope chamber without the need for solidification. Images are presented from normal and pathological thyroid specimens showing subcellular elements unavailable to the cytopathologist by light microscopy. Of 24 samples, 18 were adequate for clinical evaluation. In 16 of these 18 specimens, we could find features compatible with the final histological or cytological diagnosis (post-hoc). In two cases, the cell features were too unique to be interpretable. Because this procedure is relatively simple, there is potential for the use of this technology as an adjunct to light microscopy in clinical and research settings.
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.
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.
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.
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%).
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.
High density breast mammography has been associated with a greater risk for breast cancer and an increased likelihood of false negative results.
To assess whether the degree of mammographic breast ...density correlates with increased risk for the presence of radiographic findings requiring further histological investigation.
Included in the study were 2760 consecutive screening mammograms performed in a large volume, early detection mammography unit. All mammograms were complemented by high resolution ultrasound and interpreted by a single expert radiologist. Breast density (BD) was evaluated using a semi-quantitative 5 grade scale and grouped into low breast density (LBD) and high breast density (HBD) mammograms. Demographic and all relevant obstetric, personal and family history of breast cancer data were recorded.
Of the 2760 mammograms 2096 (76%) were LBD and 664 (24%) were HBD. Mean age of the LBD and HBD groups was 59 ± 10.5 and 50.9 ± 9.3 years respectively (P = 0001). Breast density significantly correlated with presence of mammographic findings requiring further histological assessment (8.7% and 12.3% for LBD and HBD respectively, P < 0.01). In women younger than 60 years in whom histological assessment was required due to these findings, malignant pathology was significantly more prevalent in the HBD group (2.3% and 4.1% respectively, P = 0.03). Age, parity, patient history and HBD were identified as independent risk factors for any pathological mammographic finding.
Highly dense mammography, aside from being an indicator of higher risk for breast cancer, appears to be associated with a significantly higher incidence of findings that will prompt further investigation to achieve a definite diagnosis.
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