Surgery for T4 breast carcinoma: implications for local control

Despite increasing public awareness and widespread availability of mammography, many patients will present with locally advanced breast cancers. The role of surgery remains controversial. Between 1993 and 1998, 47 of 393 (11.9%) breast cancer patients presented with T4 (inflammatory or locally advanced) carcinoma. We reviewed multimodality management, clinical response to neoadjuvant therapy, perioperative course and complications, and local control. Forty-six women and one man were diagnosed with clinical T4 breast cancer. There were 24 white and 23 African-American patients. Mean age at presentation was 54.5 (range, 31-88) years. Twenty-three patients had clinical metastases to axillary nodes, and five had distant metastases at the time of diagnosis. For these women, intent was for personal hygiene and control of pain. Neoadjuvant chemotherapy was given for 34 of 47 (72%) with 25 of 34 (73.5%) having partial or complete clinical response. There was no response or progression of disease in 9 of 34(26.5%). Forty-six patients underwent radical or modified radical mastectomy, whereas a single patient underwent breast conservation treatment. Twelve required tissue transfer for wound coverage. Although eight developed minor wound complications (cellulitis/flap separation), there were no major wound complications. Pathologically negative margins were achieved in all but one patient. To date, five women have developed local recurrence in either the chest wall (three) or axilla (two). Average time to local recurrence was 7.8 months. There is no evidence of local failure in the remaining 87 per cent. Locally advanced breast cancer is a common occurrence in certain populations. Multimodality management remains the standard of care. Surgical resection may allow for successful local control and, in certain situations, long-term cure.     

Video-assisted endoscopic thyroidectomy

BACKGROUND: Several experimental and clinical reports concerning endoscopic parathyroid surgery have appeared. However, reports concerning minimally invasive surgery for thyroid remains rare. Herein we present a new method, called video-assisted endoscopic thyroidectomy (VAET), for the management of various benign thyroid diseases. METHODS: In all, 16 consecutive patients who underwent VAET for benign thyroid diseases were retrospectively studied. The study group included nodular hyperplasia in 8 patients, follicular adenoma in 6, and Hurthle's tumor and simple cyst in 1 each. A 2 to 3 cm transverse incision was made on the suprasternal notch. The wound was deepened to expose the underlying trachea from which the plane of the thyroid fascia was accessed directly, and the working space was established with lifting method using conventional instrument. All surgical procedures could be manipulated and monitored under laparoscopy without gas insufflation. The ultrasonically activated scalpel was the principal instrument used for VAET. RESULTS: All 16 patients underwent VAET successfully without conversion to open thyroidectomy. The surgical procedures included lobectomy in 13 and extirpation in 3. The operation time ranged from 28 minutes to 5 hours (mean 1 hour, 42 minutes). For the 5 most recent cases, lobectomy took an average of 2 hours, whereas extirpation less than 40 minutes. The tumor size ranged from 3.5 cm to 8.0 cm (mean 5.8 cm). There were no surgical complications. All patients but 1 were discharged on postoperative day 2. During follow-up, all patients demonstrated euthyroid function and satisfactory cosmetic results. CONCLUSIONS: VAET emerges as a promising minimally invasive surgical technique replacing conventional thyroidectomy for benign thyroid diseases in selected cases, with the advantage of satisfactory cosmetic results.     

The impact of external feedback on computer-assisted learning for surgical technical skill training

BACKGROUND: Computer-assisted learning (CAL) offers a number of potential advantages for surgical technical skills teaching. The purpose of this study was to evaluate the impact of individualized external feedback on surgical skill acquisition when a CAL package is used for instruction. METHODS: Freshman and sophomore students participated in a 1-hour CAL session designed to teach them how to tie a two-handed square knot. One group received individualized external feedback during the session and the other group did not. Subjects were videotaped performing the skill before and after the session. The tapes were independently analyzed, in blinded fashion, by three surgeons. Three measures were obtained: the total time for the task, whether or not the knot was square, and the general quality of the performance using a rating scale. RESULTS: Data from 105 subjects were available for final analysis. For both groups there were significant increases in the proportion of knots that were square when the posttest performance was compared with the pretest performance but there was no difference between groups on this measure. Comparison of the performance scores demonstrated that both groups had a significant improvement after the session but the performance scores were significantly better in the group that had received feedback. CONCLUSIONS: Novices in both groups using CAL showed improvement in two of the outcomes measured, suggesting that subjects in both groups attained some degree of competence with this skill. The higher posttest performance score for the group receiving feedback demonstrates that external feedback results in a higher level of mastery when CAL is used to teach surgical technical skills.     

Comparison between double-filtration plasmapheresis and immunoadsorption plasmapheresis in the treatment of patients with myasthenia gravis

Two techniques for plasmapheresis are used in the treatment of myasthenia gravis (MG): immunoadsorption (IA) and double filtration (DR). This controlled study evaluated the differences between these techniques in clinical effects and serological changes. Five patients with generalized MG (clinical states IIb and III) were enrolled; each patient received IA and DF plasmapheresis on separate occasions. Immunosorba TR-350 with an affinity to acetylcholine receptor antibodies (AchRAb) was used for IA, while Evaflux 4A was used as the plasma fractionator for DF. Each course of treatment consisted of five sessions of apheresis. MG score, titers of AchRAb, immunoglobulins (IG), and plasma biochemistry were assessed by blinded examiners before and immediately after the entire course of treatment. Both treatments effectively ameliorated symptoms of MG. There were no significant changes in MG score between the two groups (IA vs. DF: 2.2 vs. 2.6, P>0.5). IA had a higher clearance rate of AchRAb than DF (66 % vs. 54 %, P<0.05), while DF removed more IgA (72 % vs. 21 %, P< 0.05) and IgM (89 % vs. 57 %, P<0.01) than did IA. Although IA removed AchRAb more effectively than DF, the clinical effects between these two treatments were similar. The titers of AchRAb cannot reflect the clinical severity. Some circulating factors other than AchRAb may contribute to the pathogenesis of MG. Received: 10 September 1999, Received in revised form: 7 February 2000, Accepted: 24 February 2000     

Recurrent corneal perforation and acute calcareous corneal degeneration in chronic graft-versus-host disease.

Keratoconjunctivitis sicca (KCS) is a common complication of graft-versus-host disease (GVHD), and may lead to corneal epithelial defect and melting. In contrast, recurrent corneal calcareous degeneration and perforation is rare. A 46-year-old woman developed chronic GVHD after bone marrow transplantation for aplastic anemia. Severe KCS with corneal melting and calcium deposits were noted in the left eye. Penetrating keratoplasty was performed because of corneal perforation, but poor re-epithelialization and calcium deposition recurred. Lamellar keratectomy and amniotic membrane transplantation (AMT) were performed, but acute calcareous degeneration developed with subsequent recurrence of corneal perforation. After regraft, AMT and tarsorrhaphy, the corneal graft remained clear for 3 months. However, breakdown of the corneal epithelium occurred 3 weeks after spontaneous separation of tarsorrhaphy. Six months later, corneal perforation recurred again along with exacerbation of GVHD. Regraft was performed, but the patient refused tarsorrhaphy and AMT. Poor re-epithelialization persisted after regraft. Corneal melting with impending corneal perforation ensued. Further corneal surgery was refused and the patient chose to undergo evisceration. This case demonstrates that the ocular complications of GVHD may be severe enough to lead to corneal perforation and calcareous degeneration that is recalcitrant to medical and surgical treatment.     

Rhodostomin inhibits thrombin-enhanced adhesion of ROS 17/2.8 cells through the blockade of alphavbeta3 integrin.

Osteosarcoma is a very malignant bone tumor which has a high metastatic potential and usually lead to poor prognosis. The adhesion of tumor cells to the endothelium or extracellular matrix (ECM) is an essential step in the metastatic cascade. We investigated the effect of thrombin on the adhesion activity of the osteosarcoma cell line, ROS 17/2.8. Incubation with the low concentrations of thrombin (0.01-5 U/ml, 5 min to 24 h) elevated the adhesion activity of ROS 17/2.8 to both human umbilical vein endothelial cells (HUVEC) and extracellular matrix, with the peak effect at the concentration of 0.5 U/ml for 30 min at 37 degrees C. The ROS 17/2.8 cells responded to thrombin by a peak effect of increased adhesion to HUVEC (5.5 folds vs. control) and fibronectin (4.8 folds) after thrombin pretreatment (0.5 U/ml, 30 min, 37 degrees C). Pretreatment with monoclonal antibodies against beta3 integrins, including anti-alphavbeta3, 10E5 and 7E3, effectively antagonized the thrombin-enhanced cell adhesion activity, whereas anti-alpha3beta1 and anti-alpha5beta1 did not antagonize the enhanced cell adhesion. Rhodostomin, an Arg-Gly-Asp (RGD)-containing snake venom peptide, and synthetic peptide RGDS also blocked the thrombin-enhanced ROS 17/2.8 cell adhesion. This study demonstrated that thrombin enhanced the cell adhesion of ROS 17/2.8 cells to HUVEC or ECM through an upregulation of beta3 integrins, and rhodostomin was a strong inhibitor on thrombin-enhanced cell adhesion, either to HUVEC or fibronectin substratum.     

Paclitaxel decreases the interstitial fluid pressure and improves oxygenation in breast cancers in patients treated with neoadjuvant chemotherapy: clinical implications.

PURPOSE: It has been hypothesized that tumors with high interstitial fluid pressure (IFP) and/or hypoxia respond poorly to chemotherapy (CT) because of poor drug delivery. Preclinical studies have shown that paclitaxel reduces the IFP and improves the oxygenation (pO(2)) of tumors. Our aim is to evaluate the IFP and pO(2) before and after neoadjuvant CT using sequential paclitaxel and doxorubicin in patients with breast cancer tumors of >/= 3 cm. PATIENTS AND METHODS: Patients were randomly assigned, according to an institutional review board-approved phase II protocol, to receive neoadjuvant sequential CT consisting of either four cycles of dose-dense doxorubicin at 60 mg/m(2) every 2 weeks followed by nine cycles of weekly paclitaxel at 80 mg/m(2) (group 1) or vice versa, with paclitaxel administered before doxorubicin (group 2). Patients were re-evaluated clinically and radiologically. The IFP (wick-in-needle technique) and pO(2) (Eppendorf) were measured in tumors at baseline and after completing the administration of the first and second drug. RESULTS: IFP and pO(2) were measured in 54 patients at baseline and after the first CT. Twenty-nine and 25 patients were randomly assigned to groups 1 and 2, respectively. Paclitaxel, when administered first, decreased the mean IFP by 36% (P = .02) and improved the tumor pO(2) by almost 100% (P = .003). In contrast, doxorubicin did not have a significant effect on either parameter. This difference was independent of the tumor size or response measured by ultrasound. CONCLUSION: Paclitaxel significantly decreased the IFP and increased the pO(2), whereas doxorubicin did not cause any significant changes. Tumor physiology could potentially be used to optimize the sequence of neoadjuvant CT in breast cancer.     

Combination bcl-2 antisense and radiation therapy for nasopharyngeal cancer.

PURPOSE: A wide variety of tumors depend on the dysregulation of Bcl-2 family proteins for survival. The resulting apoptotic block can often provide a mechanism for resistance to anticancer treatments, such as chemotherapy and radiation. This current study evaluates the efficacy of combining systemically delivered Bcl-2 phosphorothioate antisense (Bcl-2 ASO) and radiation for nasopharyngeal cancer therapy. RESULTS: Antisense uptake was unaffected by 0, 3, or 6 Gy radiation. Radiation decreased the fraction of viable C666-1 cells to 60%, with a further decrease to 40% in combination with Bcl-2 ASO. Despite a modest in vitro effect, Bcl-2 ASO alone caused the regression of established xenograft tumors in mice, extending survival by 15 days in a C666-1 and by 6 days in a C15 model. The survival times for mice treated with both Bcl-2 ASO and radiation increased by 52 days in C666-1 and by 20 days in C15 tumors. This combination resulted in a more-than-additive effect in C666-1 tumors. Less impressive gains observed in C15 tumors might be attributable to higher expression of antiapoptotic Bcl-2 family proteins and limited drug distribution in the tumor. Retreatment of C666-1 tumors with the Bcl-2 ASO-radiation combination, however, was effective, resulting in mice surviving for >80 days relative to untreated controls. CONCLUSIONS: Our results show that the Bcl-2 ASO and radiation combination is a highly potent therapy for nasopharyngeal cancer. Further examination of combination therapy with radiation and other Bcl-2 family-targeted anticancer agents in both preclinical and clinical settings is definitely warranted.