No significant improvement in therapy of pancreatic cancer has been reported over the last 25 y, underscoring the urgent need for new alternative therapies. Here, we coupled a radioisotope, 188 Rhenium, to an attenuated (at) live Listeria monocytogenes (Listeria at ) using Listeria-binding antibodies, thus creating a unique radioactive Listeria at (RL). We then demonstrated in a highly metastatic pancreatic mouse tumor model (Panc-02) that RL delivered radioactivity to the metastases and less abundantly to primary tumors in vivo, without harming normal cells. This result was possible because Listeria at was efficiently cleared by the immune system in normal tissues but not in the heavily immune-suppressed microenvironment of metastases and primary tumor. Multiple treatments with low doses of the RL resulted in a dramatic decrease in the number of metastases (∼90%) compared with control groups in the Panc-02 model. This is the first report of using live attenuated bacteria delivering a highly radioactive payload to the metastases, resulting in killing tumor cells in vivo without harming normal cells. The nontoxic RL treatment is attractive for clinical development as a therapy to prevent pancreatic cancer recurrence and metastases. P ancreatic ductal adenocarcinoma, synonymous to pancreatic cancer, is the fourth leading cause of cancer deaths. The socalled silent killer is characterized by its metastatic behavior before the primary tumor can be detected, resulting in a 5-y survival rate of only 4%. Current cancer treatments-i.e., surgery followed by radiation and/or chemotherapy-are ineffective, particularly against liver metastases. Gemcitabine and erlotinib, Food and Drug Administration-approved drugs for pancreatic cancer treatment, improve median survival by ∼6 mo in patients with advanced-stage disease (1-3), emphasizing the need for new alternative therapies for metastatic pancreatic cancer.For any anticancer approach to be effective, it needs to target metastases and/or remaining tumor cells after primary therapeutic intervention. Indeed, in most cases, cancer therapy is now highly effective in eradicating primary tumors through combinations of surgery, radiation, and adjuvant therapy. The reason that cancer remains such a formidable health problem is its capacity to recur in the form of widespread metastases, often with a fatal consequence. In a previous study, we found that a highly attenuated bacterium, Listeria monocytogenes (Listeria at ), which was originally used to deliver tumor-associated antigens into antigen-presenting cells, also infected tumor cells in vitro and in vivo (4). Although Listeria at was efficiently cleared by the immune system in the normal tissues within 3-5 d, immune suppression in the tumor microenvironment allowed these bacteria to accumulate in metastases and primary tumors and to kill tumor cells through high levels of reactive oxygen species (ROS) (4). Based on these results we hypothesized that Listeria at could be used to deliver anticancer agents, such as therapeutic ...

ObjectiveTo assess the complications of level I and II axillary lymph node dissection in the treatment of stage I and II breast cancer, with breast-conservation surgery and mastectomy. Summary Background DataThe role of axillary dissection for staging, and as an effective means of controlling regional nodal disease, has long been recognized. As small and low-grade lesions have been detected more frequently, and as its therapeutic impact has been questioned, axillary dissection has increasingly been perceived as associated with significant complications. MethodsTwo hundred patients, 112 of whom had breast-conservation surgery with axillary dissection and 88 of whom had total mastectomy with axillary dissection, were evaluated 1 year or more after surgery for arm swelling as well as nonedema complications. All patients had arm circumference measurements at the same four sites on both the operated and nonoperated sides. ResultsNo patient had an axillary recurrence. The mean difference in circumference on the nonoperated versus operated side was 0.425 cm Ϯ 1.39 at the midbiceps (p Ͻ 0.001), 0.315 cm Ϯ 1.27 at the antecubital fossa (p Ͻ 0.001), 0.355 cm Ϯ 1.53 at the midforearm (p Ͻ 0.005), and 0.055 cm Ϯ 0.75 at the wrist (n.s.). Seven patients (3.5%) had mild swelling of the hand. Heavy and obese body habitus were the only significant predictors of edema on multivariate analysis. One hundred fifty-three (76.5%) patients had numbness or paresthesias of the medial arm and/or axilla after surgery; in 125 (82%) of these, the problem had lessened or had resolved on follow-up assessment. ConclusionsThe characterization of a level I and II axillary dissection as a procedure with significant complications does not appear justified based on this experience.

Implantable limb lengthening using noninvasively adjusted telescopic nails dates back to 1983. The newest technology is the Precice (Ellipse Technologies). A retrospective study of the first 65 Precice nails was carried out for the treatment of limb length discrepancy (unilateral) and short stature (bilateral). Successful lengthening was achieved in all patients. There were numerous distraction and hardware complications. Despite these, implantable limb lengthening appears to be the direction for the future of limb lengthening.

Fourteen variables were tested for their ability to predict visceral or bony metastases in 177 patients with clinical Stage I melanoma of intermediate thickness (1.51 - 3.39 mm). A Cox multivariate analysis yielded a combination of four variables that best predicted bony or visceral metastases for these patients: 1) mitoses greater than 6/min 2 (p = 0.0007), 2) location other than the forearm of leg) p = 0.009, 3) ulceration width greater than 3 mm (p = 0.04), 4) microscopic satellites (p = 0.05). The overall prognostic model chi square was 32.40 with 4 degrees of freedom (p less than 10 (-5). Combinations of the above variables were used to separate these patients into at least two risk groups. The high risk patients had at least a 35% or greater chance of developing visceral metastases within five years, while the low risk group had greater than an 85% chance of being disease free at five years. Criteria for the high risk group were as follows: 1) mitoses greater than 6/mm 2 in at least one area of the tumor, irrespective of primary tumor location, or 2) a melanoma located at some site other than the forearm or leg and histologic evidence in the primary tumor of either ulceration greater than 3 mm wide or microscopic satellites. The low risk group was defined as follows: 1) mitoses less than or equal to 6/mm 2 and a location on the leg or forearm, or 2) mitoses less than or equal to 6/mm 2 and the absence in histologic sections of the primary tumor of both microscopic satellites and ulceration greater then 3 mm wide. The number of patients in this series who did not undergo elective regional node dissection (N = 47) was probably too small to detect any benefit from this procedure. Based on survival rates from this and other studies, it is estimated that approximately 1500 patients with clinical Stage I melanoma of intermediate thickness in each arm of a randomized clinical trial would be needed to detect an increase in survival rates from elective regional node dissection.