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Background Patients with locally advanced colon cancer (LACC) treated with surgery had a high risk of local recurrence. The outcomes can vary significantly among patients with pT3 disease. This study was undertaken to assess whether low-kilovolt (kV) x-ray intraoperative radiotherapy (IORT) can achieve promising results compared with electron beam IORT (IOERT) and whether specific subgroups of patients with pT3 colon cancer may benefit from low-kV x-ray IORT. Methods We retrospectively reviewed 44 patients with pT3 LACC treated with low-kV x-ray IORT. Clinicopathologic characteristics were analyzed to identify patients that could potentially benefit from low-kV x-ray IORT. The Kaplan-Meier survival analysis was used to assess overall survival (OS) and progression-free survival (PFS). Correlation analysis was used to discover the association of multiple factors to the results of treatment represented by the values of OS and PFS. Results The median follow-up of patients was 20.5 months (range, 6.1–38.8 months). At the time of analysis, 38 (86%) were alive and 6 (14%) had died of their disease. The 3-year Kaplan-Meier of PFS and OS for the entire cohort was 82.8% and 82.1%, respectively. At median follow-up, no in-field failure within the low-kV x-ray IORT field had occurred. Locoregional and distant failure had occurred in 2 (5%) patients each. The rate of perioperative 30-day mortality was 0%, and the morbidity rate was 11%. Five patients experienced 7 complications, including 4 early complications (30 days) and three late complications (> 30 days) leading early and late morbidity rates of 9% and 7%, respectively. Conclusion Patients with LACC who had undergone an additional low-kV x-ray IORT can achieve encouraging locoregional control, PFS, OS, and distant control without an increase in short-term or long-term complications. Low-kV x-ray IORT can be considered as part of management in pT3 LACC.

The use of biphasic cuirass ventilator supported radiation therapy has never been documented. We present the first technical report here. A 57-year-old man with obstructive sleep apnea presented with a T0N1M0 right sided, human papillomavirus related head and neck cancer diagnosed on excisional lymph node biopsy. On further workup, the cancer was found to have originated in the right tonsil and was staged as T1N1. The patient started definitive treatment with concurrent chemo-radiation therapy, but after 5 treatments was no longer able to lay in a supine position for treatment. Diagnostic imaging workup eventually revealed an idiopathic right sided hemi-diaphragm eventration. After consultation with cardiology, pulmonology, and head and neck surgery, recommendation was made for tracheostomy to tolerate supine radiotherapy position, but the patient refused. Instead, computed tomography simulation for radiotherapy replanning was performed using a combination of biphasic cuirass ventilation, home continuous positive airway pressure and oxygen. The patient then tolerated definitive treatment to a dose of 69.96 Gray in 33 fractions with concurrent chemotherapy and experienced no unexpected side effects. Although complex, daily treatment setup was consistent. Daily onboard imaging was precise and accurate. The patient continues to follow up with radiation oncology, medical oncology, and pulmonology. This is the first use of biphasic cuirass ventilator supported radiotherapy reported in the scientific literature. Although daily treatment setup is complex, its use could be considered in patients unable to tolerate radiation therapy treatment positioning as an alternative to tracheostomy.

Background Patients with locally advanced colon cancer (LACC) treated with surgery had a high risk of local recurrence. The outcomes can vary significantly among patients with pT3 disease. This study was undertaken to assess whether low-energy electronic intraoperative radiotherapy (eIORT) can achieve promising results comparing with electron beam IORT (IOERT) and whether specific subgroups of patients with pT3 colon cancer may benefit from eIORT. Methods We retrospectively reviewed 44 patients with pT3 LACC treated with eIORT. Clinicopathologic characteristics were analyzed to identify patients that could potentially benefit from eIORT. Kaplan-Meier survival analysis was used to assess overall survival (OS) and progression free survival (PFS). The log-rank test was used for the subgroup comparison. Results The median follow-up of patients was 20.5 months (range, 6.1–38.8 months). At the time of analysis, 38 (86%) were alive and 6 (14%) had died of their disease. The 3-year Kaplan-Meier of PFS and OS for the entire cohort were 82.8% and 82.1%, respectively. At median follow-up, no in-field failure within the eIORT field had occurred. Locoregional and distant failure had occurred in 2 (5%) patients each. The rate of perioperative 30-day mortality was 0% and morbidity rate was 11%. Five patients experienced 7 complications, including 4 early complications (30-d) and three late complications (>30 days) leading early and late morbidity rates of 9% and 7%, respectively. Conclusion Low-energy eIORT can be considered as part of management in pT3 LACC.

Postpartum hemorrhage is a major cause of maternal mortality. Though uncommon, uterine artery pseudoaneurysm can follow uterine dilatation and curettage (D + C) and needs to be considered in the differential diagnosis. This 30-year-old G1P1 woman presented with right upper quadrant pain and vaginal bleeding. She was afebrile but her white blood count was significantly increased (22.2×109 /L). One week prior, she had undergone a Cesarean delivery which was complicated by hemolysis, elevated liver enzymes, and low platelet count syndrome (HELLP), fetal dystocia, and chorioamnionitis. Uterine dilatation and curettage (D & C) and placement of a Bakri intrauterine balloon, performed for suspected retained products of conception, failed to control her postpartum bleeding. The patient wished to have a hysterectomy only as a last resort in order to preserve fertility. Emergency uterine artery angiography revealed a left uterine artery pseudoaneurysm and contrast extravasation. The patient was successfully treated with selective embolization. Computed tomography (CT) later revealed dehiscence of her uterine Cesarean section incision with an intra-abdominal fluid collection. This collection was drained. She also developed disseminated intravascular coagulopathy (DIC) syndrome as well as multiple pulmonary emboli which were both successfully treated. We discuss this unique case of uterine artery pseudoaneurysm with associated uterine dehiscence.

This study is designed to investigate the mechanisms underlying effects of receptor tyrosine kinase(s) on androgen receptor (AR) in castrate resistant prostate cancer (CRPC). Hormone ablation therapies remain the mainstay of treatment for metastatic prostate cancer, but disease eventually reoccurs as CRPC where AR has been reactivated despite castrate androgen levels. Amongst ways that facilitate restoration of AR activity in CRPC, receptor tyrosine kinases (RTKs) have been reported to activate AR and induce CRPC growth through as of yet unclear mechanisms. Our investigative studies revealed that lapatinib (inhibits Her2/Her3 heterodimer and EGFR) treatment inhibited endogenous AR expression and activity in C4-2 CRPC cells. Lapatinib induced destabilization and proteosomal degradation of the AR with minimal effect on AR mRNA transcript levels. To further investigate if this effect was dependent on Her2/Her3 or EGFR, an EGFR inhibitor erlotinib was used. It produced modest effects on AR, indicating that effects of lapatinib are predominantly through Her2/Her3. As AKT, a serine/threonine kinase, functions downstream of Her2/Her3, we then directly investigated the effects of AKT on AR in CRPC cells. Our studies revealed that inhibition of AKT decreased endogenous AR expression through proteosomal degradation. Moreover AKT inhibition decreased endogenous AR activity and C4-2 cell survival, indicating that AKT positively regulates AR and CRPC growth. As many groups have previously reported conflicting effects of AKT on AR, we are now focused on the molecular basis for this positive effect of AKT on AR expression and function in CRPC. Preliminary studies indicate that AKT inhibition may be decreasing levels of heat shock proteins (Hsp70, Hsp90) that serve as chaperones for cytoplasmic AR, and may by another mechanism be decreasing AR accumulation in the nucleus. We anticipate that these studies will provide a clear mechanistic view of effects of RTKs and AKT on AR in CRPC and highlight molecules that may be targeted for novel therapeutic interventions. Citation Format: Ankur Sharma, Steven P. Balk. Receptor tyrosine kinase(s) modulate androgen receptor signaling in castrate-resistant prostate cancer [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr C3.