A Prospective Trial of Single-Fraction Radiation to the Tumor Bed with a Novel Breast-Specific Stereotactic Radiation Therapy Device: The GammaPod.

Purpose: Radiation therapy for early-stage breast cancer is typically delivered in a hypofractionated regimen to the whole breast followed by a tumor bed boost. This results in a treatment course of approximately 4 weeks. In this study, the tumor bed boost was delivered in a single fraction as part of a safety and feasibility study for FDA clearance of the device. Methods and Materials: Eligible women with early-stage breast cancer underwent lumpectomy followed by radiation therapy. Patients underwent breast immobilization using a system specific to the GammaPod followed by CT simulation, boost treatment planning, and boost treatment delivery all in a single treatment day. Patients then started whole-breast radiation therapy within 1 week of the boost treatment. Patients and treatments were assessed for safety and feasibility. Acute toxicities were recorded. Results: A single-fraction boost of 8 Gy was delivered to the tumor bed before a course of whole-breast radiation. The GammaPod treatment was successfully delivered to 14 of 17 enrolled patients. Acute toxicities from all radiation therapy, inclusive of the boost and whole-breast radiation, were limited to grade 1 events. Conclusions: The GammaPod device successfully delivered a single-fraction boost treatment to the tumor bed with no change in expected acute toxicities. The results of this study led to FDA clearance of the device through the Investigational Device Exemption process at the FDA. The GammaPod is in clinical use at 4e institutions nationally and internationally, with additional sites pending in 2023.

Is oncotype DX recurrence score (RS) of prognostic value once HER2-positive and. low-ER expression patients are removed?

Oncotype DX has been criticized for not providing significantly more prognostic information than histopathologic analysis. Oncotype DX was validated in cohorts that included poor prognostic factors (HER2-positive, low-estrogen receptor [ER] expression), raising the question: if patients with known high recurrence rates are excluded, is the Recurrence Score (RS) still valid? Our purpose was to determine if RS can be predicted with readily available measures. One hundred and twenty samples from August 2006 to November 2010 that underwent Oncotype DX testing were analyzed. Data included RS, ER, progesterone receptor (PR), HER2, and Ki67 status by immunohistochemistry (IHC). IHC data were used to create two linear regression models to predict RS. SAS's JMP-7 was used for statistical analysis. When comparing Oncotype DX- and IHC-derived ER and PR values, there were 21 discordant samples. The linear regression model PRS-F created with IHC data (ER, PR, HER2, Ki67) from all samples (n = 120) had an adjusted R(2) = 0.60 indicating a good model for predicting RS. The PRS-R model was built without low-ER and HER2-positive samples (n = 110). It had an adjusted R(2) = 0.38 indicating poor prediction of RS. Oncotype DX data showed good concordance with IHC for ER- and PR-expression in this cohort. Low-ER samples had high RS. After removing low-ER and HER2-positives, calculating RS with PRS-R from remaining data showed poor predictive power for RS (adjusted R(2) = 0.38). This result questions whether RS is prognostic in this subgroup (who would most benefit from further clarification of recurrence risk) and independent of pathology, or is simply producing random RS values. Data bases available to Genomic Health can resolve this issue.

Acellular dermal matrix compared with synthetic implant material for repair of ventral hernia in the setting of peri-operative Staphylococcus aureus implant contamination: a rabbit model.

BACKGROUND: Implant infection is a common clinical complication of abdominal hernia repair. Our objectives were to determine if acellular dermal matrix (ADM) grafts resisted Staphylococcus aureus infection better (as measured by ability to reduce or clear bacterial counts) than synthetic (polytetrafluoroethylene [PTFE]) mesh when used in abdominal wall reconstruction, and to determine whether vascularization of the implant occurred. We hypothesized that the ability of the ADM grafts to vascularize and allow cellular ingrowth would allow the immune system to clear the infection better in these animals. METHODS: In New Zealand White rabbits (average weight, 3.0 kg), a full-thickness 3 x 3 cm(2) abdominal defect was created, then repaired with an interpositional implant (ADM, n = 62; PTFE, n = 57). Before skin closure, the epidermal surface of each implant was inoculated with 1 mL of S. aureus at various concentrations (10(4) colony-forming units [CFU]/mL, n = 82; 10(6) CFU/mL, n = 27; 10(9) CFU/mL, n = 10), and the rabbits were harvested at either day 7 or day 21. RESULTS: At day 7, ADM grafts inoculated with 10(4) CFU had lower counts or no bacteria (p = 0.006), fewer adhesions (p = 0.005), and fewer abscesses (p = 0.008) than PTFE grafts. By day 21, more ADM (n = 12) than PTFE (n = 0) grafts were free of bacteria (p = 0.002). Fewer rabbits with ADM grafts formed abscesses (13 vs. 19; p = 0.03). When evaluating the 7- and 21-day 10(4) CFU groups combined, a total of 15 rabbits with ADM cleared the bacteria completely vs. none of those with PTFE grafts (p < 0.001). There was no significant difference in bacterial counts or wound complications at days 7 or 21 between PTFE and ADM implants when inoculated with 10(6) CFU. All rabbits inoculated with 10(9) CFU died of sepsis within 48 h. Herniation did not occur in any of the animals. CONCLUSIONS: Our study demonstrates that ADM resists surgical site infection caused by S. aureus in an animal model without compromising the ventral hernia repair. This ability of ADM grafts to perform well in the setting of infection is most likely attributable to their capacity to vascularize and aid clearance of bacteria.

Laparoscopically assisted components separation technique for ventral incisional hernia repair.

Reconstruction of the abdominal wall to repair ventral hernias continues to pose a challenge to surgeons due to relatively high rates of recurrence and morbidity. In 1990, Ramirez pioneered a technique of components separation of the abdominal wall for ventral hernia repair. Although an effective hernia repair, the mobilization of skin and subcutaneous tissue endangers the blood supply and predisposes midline skin to necrosis. The goal of this study is to determine whether releasing incisions in the transversus abdominis fascia and posterior rectus sheath provide adequate mobilization of the abdominal wall necessary for ventral hernia repair, thus paving the way for a laparoscopic component separation technique. Ten fresh cadavers were used and one side of the abdomen underwent the conventional Ramirez components separation: midline incision, dissection of skin and subcutaneous tissue off the anterior abdominal wall, and incisions in the external oblique aponeurosis and posterior rectus sheath, while the other side received incisions in the transversus abdominis fascia and the posterior rectus sheath with no undermining of the skin. The amount of fascial translation was measured after each incision. Incising only the external oblique aponeurosis produced greater mobilization of the abdominal wall at the level of the umbilicus (P = 0.02) and anterior superior iliac spine (ASIS, P = 0.029) than releasing only transversus abdominis fascia. More importantly, there was no statistically significant difference in the amount of release produced by the complete internal-release components separation versus the conventional technique. In order to test the feasibility of performing the procedure laparoscopically, one additional cadaver underwent a laparoscopic transversus abdominis fascia release. The procedure was successful and resulted in comparable amounts of fascial release as the other 10 cadavers. From this study, it appears technically feasible to perform a laparoscopic components separation to repair a ventral hernia and the procedure produces the same amount of release as the conventional open component separation technique.

Nature of gram-negative rod antibiotic resistance during antibiotic rotation.

PURPOSE: The aim of this study was to characterize the evolution of gram-negative antibiotic resistance during a study of empiric antibiotic rotation. METHODS: We showed previously that quarterly rotation of a single antibiotic class is inferior to cycling two antibiotics per quarter for empiric treatment of gram-negative rod (GNR) infections, as evidenced by increased incidence of antibiotic-resistant GNR (rGNR) infections. Resistance patterns were examined by quantifying GNRs resistant to one or more of the following drug classes: Aminoglycosides, cephalosporins, carbapenems, fluoroquinolones, or piperacillin-tazobactam. For all rGNR isolates, the mean number of antibiotic classes to which an organism was resistant was calculated per quarter, as was the number of rGNR species. RESULTS: Single-antibiotic rotation (SAR) was associated with significant increases in the incidence of piperacillin-tazobactam (p < 0.0005) and cephalosporin (p = 0.003) resistance, reaching nearly 25% and 30% of rGNR isolates respectively, most notably during the quarter of designated cephalosporin use (VI). Multi-drug resistance emerged over time; resistant classes/resistant GNR isolates ranged from 1.2 in the dual-antibiotic rotation (DAR) to 1.9 in the SAR period (p = 0.02). Resistance was evident in an increasing number of unique GNR species. On average, 1.3 species were isolated per month in the DAR period and 3.0/month in the SAR period (p = 0.004), but proportionally, no single GNR species became significantly more resistant across time. Compared to only 5.8% in the DAR period, 29% noncompliance was observed in the SAR, with a six-fold increase in the use of nonscheduled empiric antibiotics due to the presence of an organism resistant to the scheduled rotation drug. CONCLUSIONS: A single-antibiotic rotation is associated with increased incidence and heterogeneity of resistant GNR isolates, as well as increased multiple-drug-class resistance. The attenuation of resistance observed in the single-antibiotic rotation may reflect the effect of unintended antibiotic heterogeneity driven by increasing resistance to the antibiotic class recommended for use each quarter. This suggests that reliance on a single antibiotic class for empiric treatment of GNR infection exerts sufficient pressure within the environment to encourage the development of diversified resistance, as well as cross-resistance over antibiotic classes, thus narrowing the availability of effective antibiotic treatment.