The Genomic Heritage of Lymph Node Metastases: Implications for Clinical Management of Patients with Breast Cancer

Background Metastatic breast cancer is an aggressive disease associated with recurrence and decreased survival. To improve outcomes and develop more effective treatment strategies for patients with breast cancer, it is important to understand the molecular mechanisms underlying metastasis. Methods We used allelic imbalance (AI) to determine the molecular heritage of primary breast tumors and corresponding metastases to the axillary lymph nodes. Paraffin-embedded samples from primary breast tumors and matched metastases (n = 146) were collected from 26 patients with node-positive breast cancer involving multiple axillary nodes. Hierarchical clustering was used to assess overall differences in the patterns of AI, and phylogenetic analysis inferred the molecular heritage of axillary lymph node metastases. Results Overall frequencies of AI were significantly higher (P < 0.01) in primary breast tumors (23%) than in lymph node metastases (15%), and there was a high degree of discordance in patterns of AI between primary breast carcinomas and the metastases. Metastatic tumors in the axillary nodes showed different patterns of chromosomal changes, suggesting that multiple molecular mechanisms may govern the process of metastasis in individual patients. Some metastases progressed with few genomic alterations, while others harbored many chromosomal alterations present in the primary tumor. Conclusions The extent of genomic heterogeneity in axillary lymph node metastases differs markedly among individual patients. Genomic diversity may be associated with response to adjuvant therapy, recurrence, and survival, and thus may be important in improving clinical management of breast cancer patients.     

Aminobisphosphonates Cause Osteoblast Apoptosis and Inhibit Bone Nodule Formation In Vitro

Bisphosphonates are widely used for the treatment of bone diseases associated with increased osteoclastic bone resorption. Bisphosphonates are known to inhibit biochemical markers of bone formation in vivo, but it is unclear to what extent this is a consequence of osteoclast inhibition or a direct inhibitory effect on cells of the osteoblast lineage. In order to investigate this issue, we studied the effects of various bisphosphonates on osteoblast growth and differentiation in vitro. The aminobisphosphonates pamidronate and alendronate inhibited osteoblast growth, caused osteoblast apoptosis, and inhibited protein prenylation in osteoblasts in a dose-dependent manner over the concentration range 20-100 microM. Further studies showed that alendronate in a dose of 0.1 mg/kg inhibited protein prenylation in calvarial osteoblasts in vivo, indicating that alendronate can be taken up by osteoblasts in sufficient amounts to inhibit protein prenylation at clinically relevant doses. Pamidronate and alendronate inhibited bone nodule formation at concentrations 10-fold lower than those required to inhibit osteoblast growth. These effects were not observed with non-nitrogen-containing bisphosphonates or with other inhibitors of protein prenylation and were only partially reversed by cotreatment with a fourfold molar excess of ss-glycerol phosphate. We conclude that aminobisphosphonates cause osteoblast apoptosis in vitro at micromolar concentrations and inhibit osteoblast differentiation at nanomolar concentrations by mechanisms that are independent of effects on protein prenylation and may be due in part to inhibition of mineralization. While these results need to be interpreted with caution because of uncertainty about the concentrations of bisphosphonates that osteoblasts are exposed to in vivo, our studies clearly demonstrate that bisphosphonates exert strong inhibitory effects on cells of the osteoblast lineage at similar concentrations to those that cause osteoclast inhibition. This raises the possibility that inhibition of bone formation by bisphosphonates may be due in part to a direct inhibitory effect on cells of the osteoblast lineage.     

Global left-ventricular function by tissue Doppler imaging in pediatric dialysis patients

Cardiovascular abnormalities are observed in most children with end-stage renal disease (ESRD). The aim of this study was evaluation of left-ventricular (LV) myocardial performance using tissue-Doppler imaging (TDI) in patients with ESRD. Twenty-five patients with ESRD and 25 healthy gender- and age-matched control subjects were assessed with conventional M-mode echocardiography, pulsed-wave Doppler (PWD), and TDI. Myocardial Performance Index (MPI) and LV mass index (LVMI) were calculated. MPI and conventional echo-Doppler indices were compared in the ESRD and control groups. Significant differences were present in the mean systolic and diastolic blood pressure (BP) between children with ESRD and healthy children (p = 0.007 and p < 0.001, respectively). The mean LVMI was significantly greater in the patient group (p < 0.001). The tissue-Doppler MPI of patients was significantly higher than that in healthy children (p < 0.001). LVMI was significantly correlated with systolic and diastolic BP. MPI obtained by TDI was significantly correlated with LVMI. Our study confirms that LV dysfunction is present in patients with ESRD and hypertension is an important risk factor.     

Long-term survival after a surgical resection of pulmonary metastases from gastric cancer: Report of a case

We describe a patient who survived for a prolonged period after repeated resections of pulmonary metastases from gastric cancer. A 59-year-old man underwent a distal gastrectomy for gastric cancer. A right middle lobectomy and a left lower lobectomy were performed for metastases from gastric cancer at 34 months and 82 months after the initial gastric resection, respectively. The patient died of cerebral infarction 65 months after the first lung resection, with no further relapse. To our knowledge, long-term survival after resection of pulmonary metastases from gastric cancer has only been reported in 3 patients previously. We herein review the literature and discuss the role of surgery in such patients.     

A Prospective Evaluation of Laparoscopic Versus Open Left Lateral Hepatic Sectionectomy

Background Left lateral sectionectomy is one of the most commonly performed laparoscopic liver resections, but limited clinical data are actually available to support the advantage of laparoscopic versus open-liver surgery. The present study compared the short-term outcomes of laparoscopic versus open surgery in a case-matched analysis. Materials and Methods Surgical outcome of 20 patients who underwent left lateral sectionectomy by laparoscopic approach (LHR group) from September 2005 to January 2007 were compared in a case-control analysis with those of 20 patients who underwent open left lateral sectionectomy (OHR group). Both groups were similar for: tumor size, preoperative laboratory data, presence of cirrhosis, and histology of the lesion. Surgical procedures were performed in both groups combining the ultrasonic dissector and the ultrasonic coagulating cutter without portal clamping. Results Compared with OHR, the LHR group had a decreased blood loss (165 mL versus 214 mL, P = 0.001), and earlier postoperative recovery (4.5 versus 5.8 days, P = 0.003). There were no significant differences in terms of surgical margin and operative time. Morbidity was comparable between the two groups, but two cases of postoperative ascites were recorded in two cirrhotic patients in the OHR. Major complications were not observed in either groups. Conclusions Laparoscopic resection results in reduced operative blood loss and earlier recovery with oncologic clearance and operative time comparable with open surgery. Laparoscopic liver surgery may be considered the approach of choice for tumors located in the left hepatic lobe.     

Iatrogenic Injury of the Intrathoracic Esophagus Sustained During a Gastric Banding Procedure

The wide diffusion of laparoscopic adjustable gastric banding as a common surgical procedure for the treatment of morbidly obese patients can be attributed not only to the easy surgical technique, the ability to caliber the stoma, and the potential for reversibility, but also to the fact that this procedure is associated with a low rate of immediate postoperative complications compared to other more complex bariatric procedures. Herein reported is the case of a 63-year-old morbidly obese woman who sustained an iatrogenic injury of the intrathoracic esophagus during a laparoscopic adjustable gastric banding procedure. The putative mechanism of this previously unreported complication of laparoscopic adjustable gastric banding and the therapeutic options are discussed. The patient was initially treated with left pleural cavity drainage, antibiotics and the placement of an endoscopic silicone covered stent to cover the esophageal tear. Nine days later she underwent surgery through left thoracotomy due to the persistence of the esophageal leak. Esophageal perforation is a potentially life- threatening complication that may occur during a laparoscopic gastric banding procedure. The conservative treatment with an endoscopic stent should be reserved to patients with no signs of progressive systemic inflammation and include the drainage of the pleural cavity and the mediastinum, the endoscopic lavage and debridement. Standard surgical treatment with direct repair should not be retarded in case of persistence of the leak.     

The multifilament polypropylene tape erosion trouble: tape structure vs surgical technique. Which one is the cause?

This study was designed to clarify whether the structure of multifilament tape or the surgical technique is associated with vaginal erosions. Patients were randomized into two groups: in group 1, formed from the patients who were operated with the technique “setting the tape loosely leaving a scissor tip gap between the tape and the urethra,” and in group 2, formed from the patients who were operated with the technique “setting the tape actually touched the urethra and covering the tape by the adjacent pubocervicovaginal fascia with the aid of a suture.” After 4-year follow-up, it was found that the erosion rate was very high in group 1 (13.6%). We conclude that the high erosion rate seen in multifilament tapes is associated with the surgical technique that is used, not the structure of the multifilament tape.     

The Effect of <Emphasis Type="Italic">N</Emphasis>ω-Nitro-<Emphasis Type="SmallCaps">l</Emphasis>-Arginine Methyl Ester and <Emphasis Type="SmallCaps">l</Emphasis>-Arginine on Lung Injury Induced by Abdominal Aortic Occlusion–Reperfusion

Purpose

The aim of this study was to examine the effects of Nω-nitro-l-arginine methyl ester (l-NAME) and l-arginine on lung injury after aortic ischemia–reperfusion (IR).

Methods

Twenty-four Wistar-Albino rats were randomized into four groups (n = 6) as follows: Control (sham laparotomy), Aortic IR (30?min ischemia and 120?min reperfusion), l-Arginine (intraperitoneal 100?mg?kg<συπ>?1 live weight)+aortic IR, and l-NAME (intraperitoneal 10?mg?kg<συπ>?1 live weight)+aortic IR. In the lung specimens, the tissue levels of malondialdehyde (MDA), vascular endothelial growth factor (VEGF), and nitric oxide (NO) were measured and a histological examination was done.

Results

Aortic IR increased MDA, VEGF, and NO. l-Arginine further significantly increased MDA and NO, and decreased VEGF (P < 0.05 vs aortic IR). l-NAME significantly decreased MDA and NO (P < 0.05 vs l-arginine+aortic IR) and increased VEGF (P < 0.05 vs other groups). A histological examination showed the aortic IR to significantly increase (P < 0.05 vs control) while l-arginine also further increased (P > 0.05 vs aortic IR), whereas l-NAME caused a significant decrease in pulmonary leukocyte infiltration (P < 0.05 vs aortic IR).

Conclusions

Our results indicate that l-arginine aggravates the lung injury induced by aortic IR, while l-NAME attenuates it.

     

A Significant Correlation between Nuclear CXCR4 Expression and Axillary Lymph Node Metastasis in Hormonal Receptor Negative Breast Cancer

Background and objectives In breast cancer, the expression pattern of CXCR4 may be correlated with the degree of axillary lymph node involvement. The aim of this study was to evaluate the contributing factors that contribute to the correlation between CXCR4 expression and axillary lymph node metastasis in breast cancer. Methods Between August 1997 and August 2002, sections of paraffin-embedded tissue were obtained from 107 patients who received optimal treatment for breast cancer. The expression of CXCR4 was evaluated by immunohistochemical staining. Results A significant correlation was found in the expression of nuclear CXCR4 and lymph node metastasis (P = 0.03). We found a significant correlation between a high nuclear expression of CXCR4 and axillary lymphatic metastasis in estrogen and progesterone receptor negative breast cancer (P = 0.01 and P = 0.01). There was a significant correlation between the high expression of nuclear CXCR4 and axillary lymphatic metastasis in comparisons between positive estrogen and/or progesterone receptor expression and negative expression (P = 0.02). Conclusions Our results showed that high expression of nuclear CXCR4 was significantly correlated with lymph node metastasis in breast cancer. The high expression of nuclear CXCR4 in hormone receptor negative breast cancer was associated with a high possibility of lymph node metastasis.     

Benign osteoblastoma of the odontoid process of the axis with secondary aneurysmal bone cyst component: a case report

The authors report their experience on one patient with osteoblatoma of the odontoid process of the axis with secondary aneurysmal bone cyst. According to their knowledge, this is the first case, reported in the literature, of this kind of lesion in that particular anatomical region. Because of the rarity of this lesion, it was difficult to have a certain preoperative diagnosis. Therefore, the patient underwent a biopsy via a transoral route. The biopsy was performed over the noncalcified component of the lesion. The intraoperative histological examination showed the benign nature of the lesion. Thereafter, the lesion was totally removed, succeeding in preserving the remaining part of the odontoid process and the anterior arch of C1. In the follow-up, there was no evidence of cranio-vertebral instability. The histological examination revealed an osteoblastoma of the odontoid process of the axis with a secondary aneurysmal bone cyst. To the best of our knowledge, this is the first case reported in the literature.