Nonsteroidal anti-inflammatory drug use associated with reduced incidence of adenocarcinomas of the esophagus and gastric cardia that overexpress cyclin D1: a population-based study.

This study was undertaken to determine whether selected risk factors for esophageal and gastric cancer are associated with tumors that overexpress cyclin D1. Archived tumor tissue was available for 630 esophageal and gastric cancer patients who participated in a population-based case-control study. Patients were categorized into case groups based on whether protein overexpression of the cyclin D1 gene, as assessed by immunohistochemistry, was present (cyclin D1+, n = 285) or not (cyclin D1-, n = 345) in the tumor. The distribution of risk factors in each of these case groups was then compared with the distribution among the 695 controls. Multivariate-adjusted odds ratios (OR) for esophageal adenocarcinoma were reduced in relation to use of aspirin and other nonsteroidal anti-inflammatory drug (NSAID) use but only among patients with cyclin D1+ tumors (0.45, 95% confidence interval [CI] = 0.26, 0.79) and not among those with cyclin D1- tumors (1.12, 95% CI = 0.67, 1.86). A similar pattern was observed for gastric cardia adenocarcinomas. In contrast, ORs for esophageal squamous cell carcinoma and noncardia gastric adenocarcinomas in relation to NSAID use were reduced, regardless of cyclin D1 status. ORs did not vary with cyclin D1 status in relation to alcohol, body size, or cigarette smoking, with the following exception; for noncardia gastric adenocarcinomas the cyclin D1- tumors showed a 2-fold elevation in the OR with ever smoking. These data suggest that the reduction in risk associated with NSAID use may be restricted to those esophageal and gastric cardia adenocarcinomas that overexpress cyclin D1.     

Evaluation of biologic end points and pharmacokinetics in patients with metastatic breast cancer after treatment with erlotinib, an epidermal growth factor receptor tyrosine kinase inhibitor.

PURPOSE: To evaluate changes in epidermal growth factor receptor (EGFR) phosphorylation and its downstream signaling in tumor and surrogate tissue biopsies in patients with metastatic breast cancer treated with erlotinib, an EGFR tyrosine kinase inhibitor, and to assess relationships between biomarkers in tumor and normal tissues and between biomarkers and pharmacokinetics. PATIENTS AND METHODS: Eighteen patients were treated orally with 150 mg/d of erlotinib. Ki67, EGFR, phosphorylated EGFR (pEGFR), phosphorylated mitogen-activated protein kinase (pMAPK), and phosphorylated AKT (pAKT) in 15 paired tumor, skin, and buccal mucosa biopsies (at baseline and after 1 month of therapy) were examined by immunohistochemistry and analyzed quantitatively. Pharmacokinetic sampling was also obtained. RESULTS: The stratum corneum layer and Ki67 in keratinocytes of the epidermis in 15 paired skin biopsies significantly decreased after treatment (P = .0005 and P = .0003, respectively). No significant change in Ki67 was detected in 15 tumors, and no responses were observed. One was EGFR-positive and displayed heterogeneous expression of the receptor, and 14 were EGFR-negative. In the EGFR-positive tumor, pEGFR, pMAPK, and pAKT were reduced after treatment. Paradoxically, pEGFR was increased in EGFR-negative tumors post-treatment (P = .001). Although markers were reduced in surrogate and tumor tissues in the patient with EGFR-positive tumor, no apparent associations were observed in patients with EGFR-negative tumor. CONCLUSION: Erlotinib has inhibitory biologic effects on normal surrogate tissues and on an EGFR-positive tumor. The lack of reduced tumor proliferation may be attributed to the heterogeneous expression of receptor in the EGFR-positive patient and absence of target in this cohort of heavily pretreated patients.     

The effect of megestrol acetate on growth of HepG2 cells in vitro and in vivo.

PURPOSE: Hepatocellular carcinoma (HCC) is generally considered as a sex hormone-dependent tumor, and hormonal therapy has been proposed as a strategy for the treatment of HCC. The aim of the study is to investigate the effect of megestrol acetate, a synthetic progesteronal agent, on growth of HepG2 cells in vitro and in vivo. EXPERIMENTAL DESIGN: Cell growth in vitro was assessed by a colormetric method, and cell growth in vivo was assessed by tumor volumetrics. RESULTS: Megestrol acetate was shown to inhibit the growth of HepG2 cells in vitro in dose- and time-dependent manners with an IC (50) of 260 microm (24-h incubation). The growth of HepG2 cell-transplanted tumors in nude mice was also inhibited by i.p. injection of megestrol acetate (10 mg/kg/day). The tumor volumes of the megestrol acetate-treated group regressed to 59% of controls by week 6 and to 41% of controls by week 13. Apoptosis following G(1) arrest was observed in megestrol acetate-treated cells and may be a mechanism through which megestrol acetate inhibits HepG2 cells. Megestrol acetate was also demonstrated to have a beneficial effect on the weight gain of tumor-bearing nude mice, and the mean weight of the megestrol acetate-treated animals was higher than that of controls from week 4 of the treatment period, and the differences were statistically significant in week 5 and 6 (P < 0.05, compared with controls). No significant survival advantage was, however, demonstrated in the treatment group. CONCLUSIONS: This study showed that megestrol acetate inhibited the growth of HepG2 cells grown in vitro and in vivo. These data provide useful information for clinical study of megestrol acetate for the treatment of HCC.     

Computed tomography (CT) evaluation of breast cancer patients with osteolytic bone metastases undergoing palliative radiotherapy—a feasibility study

Twenty-five patients with osteolytic metastases had computed tomography (CT) scans before and 3 months after palliative radiotherapy. The median % density change following single 8 Gy, 20 Gy/5#, 30 Gy/10# were: 128 (range 98–255), 141 (79–342), and 145 (65–235), respectively. It is feasible to evaluate remineralization of osteolytic lesions with palliative radiotherapy.     

Expression of nm23 protein in human osteosarcoma in relationship with early metastasis

Nm23 protein expression was analyzed by immunohistochemical staining using formalin-fixed, paraffin-embedded sections from 39 cases with osteosarcomas and compared with the histologic findings and early metastasis for the purpose of detecting nm23 expression in osteosarcoma and elucidating the clinical significance of its expression. Immunoreactivity of nm23 protein was detected in 48.7% of the total cases. There was no statistical difference between nm23 expression and early metastasis, but there was a trend for cases with nm23 expression to progress to early metastasis within 1 year after operation. The role of nm23 as a tumor metastasis suppressor in osteosarcomas appeared less prominent.     

Laparoscopic live donor nephrectomy: outcomes equivalent to open surgery

A shortage of kidney donors has contributed to the interest in laparoscopic live-donor nephrectomy. Three transperitoneal ports are used, as is an AESOP robot. To maintain urine flow, the donor is kept volume expanded during the procedure, and the pneumoperitoneum pressure is minimized. The most critical and hazardous part of the surgery is dissection of the renal artery and vein. Abundant periureteral tissue should be left to protect the blood supply. Harvest of the right kidney is more difficult. Placing the extraction incision in the right upper quadrant and using a Satinsky clamp instead of a stapling device at the origin of the renal vein will provide maximum venous length and help prevent postoperative thrombosis of the allograft. In the first 175 laparoscopic renal harvest procedures at Johns Hopkins, the complication rate was 14%, the rate of open conversion was 2%, and 3% of the patients required transfusions. These rates improved with experience. There was no significant difference in the performance of the allografts or the recovery of the recipients from what is seen after open kidney harvest. Wider acceptance of laparoscopic renal harvest will increase the number of donors and will be helped by development of methods and devices that shorten the learning curve.     

Effect of adult microsurgical varicocelectomy on testicular volume

OBJECTIVES: To re-examine the potential influence of varicocelectomy on testicular volume using scrotal ultrasonography, because it has been reported that total testicular volume (assessed by physical examination) increases after adult varicocele ligation. METHODS: A retrospective review of the testicular volume and semen parameters of 61 men who underwent microsurgical varicocelectomy between 1996 and 1998 was performed. Ultrasound-derived testicular volumes and total motile sperm counts were compared before varicocelectomy and at a mean of 7.2 months postoperatively. RESULTS: Bilateral varicocelectomy was performed in 22 men; 39 men underwent a left-sided procedure only. Overall, no significant change was found in the mean total testicular volume after varicocelectomy compared with preoperatively (24.0 versus 23.9 mL, respectively; P = 0.74). Similarly, the testicular volumes did not change significantly after left or bilateral varicocelectomy (P >0.05). Overall, the mean total motile sperm count increased significantly after varicocelectomy (17. 9 to 25.4, P = 0.05). CONCLUSIONS: This was the first study to examine the effect of adult varicocelectomy on testicular volume using ultrasound-derived measurements of volume. Unlike previous findings, our data suggest that although adult varicocelectomy improves semen quality in most infertile men, it does not result in a significant increase in testicular volume.     

Nasal Reconstruction Using a Combination of Alloplastic Materials and Autogenous Tissues: A Surgical Alternative

Re-creation of a functional and aesthetically acceptable nose after partial nasal defect requires accurate reproduction of nasal lining, support, and coverage. Most authors recommend an approach to reconstruction with cantilevered bone grafting and paramedian forehead flap placement. The authors propose an alternative approach for selected patients with total or near-total nasal defects combining both alloplastic and autogenous tissues. This method uses vitallium or titanium mesh for the dorsal framework formation, tissue-expanded paramedian forehead flap for soft tissue coverage, and composite chondrocutaneous auricular grafts for tip reconstruction. Nine individuals underwent nasal reconstruction using this method. The indications, details, and potential advantages of this technique are described with accompanying photographic results. A flexible approach using a combination of alloplastic materials and autogenous tissues provides additional reconstructive options for individuals with total or near-total nasal defects.     

Detection of Serum Transforming Growth Factor-α in Patients of Primary Epithelial Ovarian Cancers by Enzyme Immunoassay

Transforming growth factor-α (TGF-α) is a potent mitogenic polypeptide. It is secreted by a variety of transformed cells and tumors, modifying tumor growth through autocrine or paracrine mechanism. In the present study, serum levels of TGF-α were determined by enzyme-linked immunosorbent assay (ELISA) in 27 normal females, 116 patients with benign ovarian tumors, and 42 patients with epithelial ovarian cancers (10 with stage I, 7 with stage II, 19 with stage III, and 6 with stage IV). The ELISA assay could detect a minimum level of serum TGF-α concentration at 10 pg/ml. Serum samples were obtained from normal females and from patients with benign or malignant ovarian tumors before initial surgery. The detectable rates were 11% (3/27) in normal females, 28% (32/116) in benign ovarian tumors, and 62% (26/42) in ovarian cancers. The detectable rates in serous and endometrioid ovarian cancers were 71 and 70%, respectively, which were higher than the rate of 33% in mucinous type. However, there was no obvious relationship between the detectability of serum TGF-α and the stages of ovarian cancers. The mean concentration of TGF-α in ovarian cancer was 159.8 pg/ml, which was significantly higher than 27.7 pg/ml in benign ovarian tumors (P< 0.001) as well as 15 pg/ml in normal females (P< 0.001). The mean concentrations of serum TGF-α in stages I to IV ovarian cancers were 133.5, 96.2, 194.8, and 178.3 pg/ml, respectively. The mean concentration of serum TGF-α in any two stages of ovarian cancers was not statistically different. In conclusion, measurement of serum TGF-α can be used as a supplementary tumor marker to differentiate a malignant ovarian tumor from a benign one. However, the concentration of serum TGF-α has no special relation with the stage of ovarian cancer itself. Because of the small number of stage I ovarian cancers with detectable TGF-α in the present investigation, it would probably not be feasible to differentiate a stage I ovarian cancer from a benign ovarian tumor based only on the level of TGF-α in serum.