Prognostication and optimal criteria of circumferential margin involvement for esophageal cancer after chemoradiation and esophagectomy.

Purpose: Circumferential radial margin (CRM) involvement by tumor after resection for esophageal cancer has been suggested as a significant prognostic factor. However, the prognostic value of CRM involvement after surgery with neoadjuvant concurrent chemoradiotherapy (CCRT) is unclear. This study aimed to evaluate the prognostic value of and survival outcomes in CRM involvement as defined by the Royal College of Pathologists (RCP) and the College of American Pathologists (CAP) for patients with esophageal cancer undergoing neoadjuvant CCRT and esophagectomy. Methods: A total of 299 patients with esophageal cancer who underwent neoadjuvant CCRT followed by esophagectomy between 2006 and 2016 were enrolled in our study. The CRM status of the specimens obtained was determined pathologically according to both the CAP and RCP criteria. Survival analyses were performed and compared according to the two criteria. Results: Positive CRM was found in 102 (34.1%) and 40 (13.3%) patients according to RCP and CAP criteria, respectively. The overall and progression-free survival rates were significantly lower in the CRM-positive group than in the CRM-negative group according to both the RCP and CAP criteria. However, under multivariate analysis, in addition to pathological T and N staging of the tumor, only CAP-defined CRM positivity was a significant prognostic factor with adjusted hazard ratios of 2.64 (1.56-4.46) and 2.25 (1.34-3.78) for overall and progression-free survival, respectively (P < 0.001). Conclusion: In patients with esophageal cancer undergoing neoadjuvant CRT followed by esophagectomy, CAP-defined CRM positivity is an independent predictor of survival. Adjuvant therapy should be offered to patients with positive CRM.

Propensity score matching analysis comparing radical prostatectomy and radiotherapy with androgen deprivation therapy in locally advanced prostate cancer.

To compare clinical outcomes between the use of robotic-assisted laparoscopic radical prostatectomy (RP) and radiotherapy (RT) with long-term androgen deprivation therapy (ADT) in locally advanced prostate cancer (PC), 315 patients with locally advanced PC (clinical T-stage 3/4) were considered for analysis retrospectively. Propensity score-matching at a 1:1 ratio was performed. The median follow-up period was 59.2 months (IQR 39.8-87.4). There were 117 (37.1%) patients in the RP group and 198 (62.9%) patients in the RT group. RT patients were older and had higher PSA at diagnosis, higher Gleason score grade group and more advanced T-stage (all p < 0.001). After propensity score-matching, there were 68 patients in each group. Among locally advanced PC patients, treatment with RP had a higher risk of biochemical recurrence compared to the RT group. In multivariate Cox regression analysis, treatment with RT plus ADT significantly decreased the risk of biochemical failure (HR 0.162, p < 0.001), but there was no significant difference in local recurrence, distant metastasis and overall survival (p = 0.470, p = 0.268 and p = 0.509, respectively). This information supported a clinical benefit in BCR control for patients undergoing RT plus long-term ADT compared to RP.

Blm-s, a BH3-only protein enriched in postmitotic immature neurons, is transcriptionally upregulated by p53 during DNA damage.

Programmed cell death is a pivotal process that regulates neuronal number during development. Key regulators of this process are members of the BCL-2 family. Using mRNA differential display, we identified a Bcl-2 family gene, Blm-s (Bcl-2-like molecule, short form), enriched in postmitotic neurons of the developing cerebral cortex. BLM-s functions as a BH3-only apoptosis sensitizer/derepressor and causes BAX-dependent mitochondria-mediated apoptosis by selectively binding to prosurvival BCL-2 or MCL-1. When challenged with γ-irradiation that produces DNA double-strand breaks (DSBs), Blm-s is transcriptionally upregulated in postmitotic immature neurons with concurrently increased apoptosis. RNAi-mediated depletion of Blm-s protects immature neurons from irradiation-induced apoptosis. Furthermore, Blm-s is a direct target gene of p53 and AP1 via the ataxia telangiectasia mutated (ATM)- and c-Jun N-terminal kinase (JNK)-signaling pathways activated by DSBs. Thus, BLM-s is likely an apoptosis sensor activated by DSBs accumulating in postmitotic immature neurons.

Polyelectrolyte enhanced ultrafiltration (PEUF) for the removal of Cd(II): effects of organic ligands and solution pH.

This study focused on the effects of pH and organic ligands, namely ethylenediaminetetraacetic acid (EDTA), nitrilotriacetic acid (NTA), and citric acids, on the removal and recovery of Cd(II) in polyelectrolyte enhanced ultrafiltration (PEUF). Polyethylenimine (PEI), which can bind with both positively charged metal ions by coordination bonding and negatively charged ligand-metal complexes by charge attraction, was employed as a chelating polymer. The removal and recovery of Cd species was greatly dependent on the chemistry of organic ligands according to solution pH, particularly being related to the distribution of Cd-ligand complexes at different pH levels. In the presence of EDTA, the dominant Cd species are negatively charged Cd(EDTA)(2-) and CdH(EDTA)(-) over the range of pH levels investigated, interacting with PEI via electrostatic attraction and being less pH dependent. On the other hand, the pH effects of both NTA and citric acid systems are similar to that for the system without organic ligands. This was associated with the fact that free Cd ions were predominant at the acidic pH range in both NTA and citric acid systems.

Vascularity change and tumor response to neoadjuvant chemotherapy for advanced breast cancer.

For advanced breast cancer with severe local disease (ABC) (stage III/IV), neoadjuvant chemotherapy improves local control and surgical outcome. However, about approximately 20 to 30% of advanced cancers show either no or poor response to chemotherapy. To prevent unnecessary treatment, a capability of predicting clinical response to neoadjuvant chemotherapy of ABC is highly desirable. Vascularity index (VI) of breast cancers was derived from the quantification results in 30 ABC patients by using power Doppler sonography. Power Doppler sonography evaluation was performed every one to two weeks during chemotherapy. The overall response rate for 30 advanced patients tested was 70%, when 50% or more reduction in tumor size was the objective clinical response. Chemotherapy response was unrelated to the original tumor size (p = 0.563) or chemotherapy agents used (p = 0.657). The median VI for all 30 patients was 4.99%. The response rates for hypervascular tumors vs. hypovascular tumors, based on initial median value, were 86.7% and 53.3%, respectively (p = 0.109). The average VIs in responders and nonresponders were 7.67 +/- 4.77% and 4.01 +/- 3.82% (p = 0.052). There was a tendency for responders who have a relatively high initial vascularity. The VI change in responder group shows a pattern of initial increasing in vascularity followed by decreasing in vascularity. All patients (17/17) with a VI increment of >5% during chemotherapy had good chemotherapy response, whereas in patients with a VI increment of <5%, the response rate was 30.8% (4/13) (p < 0.001). For patients with a peak VI of >10% during chemotherapy, the response rate was 94.1% (16/17). However, in patients with a peak VI of <10%, the response rate was 38.5% (5/13) (p = 0.001). This prediction was made mostly within one month (25.47 +/- 12.96 d for VI increments >5% and 25.44 +/- 12.41 d for VI increased to >10%). In the meantime, the differences in size reduction shown in B-mode sonography were insignificant between responders and nonresponders (patient group with VI increment >5%, p = 0.308; patient group with peak VI >10%, p = 0.396). In conclusion, we propose that VI as determined by using power Doppler sonography is a good and inexpensive clinical tool for monitoring vascularity changes during neoadjuvant chemotherapy in ABC patients. Two parameters--VI increment >5% and peak VI >10%--are potential early predictors for good responses to neoadjuvant chemotherapy within one month in patients with ABC.

Desmoid tumor of the head and neck.

BACKGROUND: [corrected] Desmoid tumors are rare benign tumors but have a tendency toward local recurrence after resection because of their infiltrative growth and frequent entrapment of vital structures in the head and neck region. We report 24 desmoid tumors of the head and neck and propose a reasonable approach in the management of such cases. METHODS: Twenty-four patients (9 male and 15 female; median age, 33 years; range, 0-66 years) with a desmoid tumor of the head and neck (neck, 15 patients; head, 9 patients) treated from 1990 to 2004 were retrospectively analyzed. The size ranged from 0.5 to 13 cm in diameter (mean, 3.6 cm). In the neck, 8 tumors were around the superficial layer of deep cervical fascia, whereas 4 tumors of the neck involved the prevertebral fascia and 2 involved brachial plexus. RESULTS: Twenty patients received complete resection of the tumor, but the section margin was positive in 8 patients, of which 6 patients remained free of disease in a period of 13 to 105 months. Three patients, including 2 with positive section margin and 1 with negative margin, developed recurrences, which were successfully removed again. Two patients underwent partial resection of the tumor because of brachial plexus involvement. One of them achieved regression after postoperative radiotherapy and the other had spontaneous regression. The hypopharygneal tumor in a newborn had spontaneously complete regression, and tracheostomy was closed at the age of 6 years. One patient remained with stable disease for 14 months after biopsy of the tumor without excision. CONCLUSION: The overall prognosis is still good despite frequent incomplete resection. Surgical resection of the tumor with close observation is suggested even if the section margin is positive. If a desmoid tumor cannot be removed grossly, regression or arrested growth of the remaining tumor is expected. Radiotherapy might be reserved for a growing tumor.

Arsenic trioxide prevents radiation-enhanced tumor invasiveness and inhibits matrix metalloproteinase-9 through downregulation of nuclear factor kappaB.

Arsenic trioxide (ATO) has been implicated as a promising anticancer agent by inhibiting cell growth and inducing apoptosis in certain types of cancer cells. This study explored the antimetastasis property of arsenic, drew potential link between arsenic use and radiotherapy, and uncovered the specific mechanisms underlying these remarkable responses. Using gelatin invasion assay and intravasation assay, we report the novel finding that low-dose ATO (1 muM) reduced the intrinsic migration ability of HeLa cells and significantly inhibited radiation-promoted tumor invasive potential of CaSki cells without inducing apoptotic cell death. Using the murine Lewis lung carcinoma model, the control animals and ATO treatment animals (1 mg/kg i.p., twice weekly) displayed similar in vivo growth kinetics, whereas the radiation (30 Gy in one fraction) and concurrent treatment groups showed considerable growth inhibition. Importantly, although concurrent treatment did not enhance the effectiveness of radiation therapy to the primary tumor, further examination of the lungs revealed that all animals succumbed to radiation-accelerated lung metastases could be effectively treated by combination of ATO and radiation. Radiation-induced matrix metalloproteinase-9 (MMP-9) expression was significantly inhibited by ATO using sequential analysis of the expression of MMPs in xenografts. Supporting this observation, ATO directly downregulates radiation-induced MMP-9 mRNA expression by inhibiting nuclear factor kappaB activity in human cervical cancer cells. In sum, concurrent arsenic-radiation therapy not only achieves local tumor control but also inhibits distant metastasis. Experimental results of this study highlight a novel strategy in cancer treatment.