A prospective comparison of the prognostic value of tumor- and patient-related factors in patients undergoing potentially curative surgery for pancreatic ductal adenocarcinoma.

BACKGROUND: Outcome prediction after resection with curative intent for pancreatic ductal adenocarcinoma remains a challenge. There is increasing evidence that the presence of an ongoing systemic inflammatory response is associated with poor outcome in patients undergoing resection for a variety of common solid tumors. Our aim was to prospectively evaluate the prognostic value of tumor- and patient-related factors including the systemic inflammatory response in patients undergoing potentially curative surgery for pancreatic ductal adenocarcinoma of the head of pancreas. METHODS: The prognostic impact of tumor factors such as stage and host factors, including the systemic inflammatory response (modified Glasgow Prognostic Score [mGPS]), were evaluated in a prospective study of 135 patients who underwent elective pancreaticoduodenectomy for pancreatic ductal adenocarcinoma from January 2002 to April 2009. RESULTS: In addition to the established tumor-related pathological factors (in particular margin involvement; hazard ratio [HR] 2.82, 95% confidence interval [CI] 1.65-4.84, P < 0.001), an elevated mGPS (HR 2.26, 95% CI 1.43-3.57, P < 0.001) was independently associated with lower overall survival after pancreaticoduodenectomy. Additionally, in an adjuvant therapy subgroup of 74 patients, both margin involvement and an elevated mGPS remained independently associated with reduced overall survival. CONCLUSIONS: We have prospectively validated the influence of tumor-related and patient-related factors. Margin involvement and the preoperative mGPS were the most important determinants of overall survival in patients undergoing potentially curative pancreaticoduodenectomy. Furthermore, both had independent prognostic value in those patients receiving adjuvant chemotherapy. In the future, this may be considered a stratification factor for entry onto therapeutic trials.

DNMT3B Oncogenic Activity in Human Intestinal Cancer Is Not Linked to CIMP or BRAFV600E Mutation.

Approximately 10% of human colorectal cancer (CRC) are associated with activated BRAFV600E mutation, typically in absence of APC mutation and often associated with a CpG island methylator (CIMP) phenotype. To protect from cancer, normal intestinal epithelial cells respond to oncogenic BRAFV600E by activation of intrinsic p53 and p16-dependent tumor suppressor mechanisms, such as cellular senescence. Conversely, CIMP is thought to contribute to bypass of these tumor suppressor mechanisms, e.g. via epigenetic silencing of tumor suppressor genes, such as p16. It has been repeatedly proposed that DNMT3B is responsible for BRAFV600E-induced CIMP in human CRC. Here we set out to test this by in silico, in vitro, and in vivo approaches. We conclude that although both BRAFV600E and DNMT3B harbor oncogenic potential in vitro and in vivo and show some evidence of cooperation in tumor promotion, they do not frequently cooperate to promote CIMP and human intestinal cancer.

Perception of the voicing distinction in speech produced during simultaneous communication.

UNLABELLED: This study investigated the perception of voice onset time (VOT) in speech produced during simultaneous communication (SC). Four normally hearing, experienced sign language users were recorded under SC and speech alone (SA) conditions speaking stimulus words with voiced and voiceless initial consonants embedded in a sentence. Twelve hearing-impaired listeners participated, with three of them randomly assigned to audit the speech sample provided by each one of the four speakers under the SC and SA conditions. In addition, 24 normal hearing listeners were randomly assigned to audit the speech samples produced by the four speakers under the SC and SA conditions, three listeners in noise and three listeners in filtered listening conditions for each of the four speakers. Although results indicated longer sentence durations for SC than SA, results showed no difference in the perception of the voicing distinction for speech produced during SC versus speech produced during SA under either the noise or filtered listening condition, or any difference in perception for the hearing-impaired listeners. This conclusion is consistent with previous research indicating that temporal alterations produced by SC do not produce degradation of temporal or spectral cues in speech or disruption of the perception of specific English phoneme segments. LEARNING OUTCOMES: As a result of this activity, the participant will be able to: (1) describe simultaneous communication; (2) explain the role of simultaneous communication in communication with persons who are hearing-impaired; (3) discuss methods of measuring perception of voice onset time with hearing-impaired listeners and with hearing listeners under filtered and noise conditions; and (4) specify the ability of listeners to perceive the voicing distinction in speech produced during simultaneous communication.

Intelligibility of speech produced during simultaneous communication.

UNLABELLED: This study investigated the overall intelligibility of speech produced during simultaneous communication (SC). Four hearing, experienced sign language users were recorded under SC and speech alone (SA) conditions speaking Boothroyd's (1985) forced-choice phonetic contrast material designed for measurement of speech intelligibility. Twelve hearing-impaired listeners participated, with three of them randomly assigned to audit the speech sample provided by each one of the four speakers under the SC and SA conditions. Although results indicated longer sentence durations for SC than SA, results showed no difference in the overall intelligibility of speech produced during SC versus speech produced during SA, nor any difference in pattern of phonetic contrast recognition errors during SC. This conclusion is consistent with previous research indicating that temporal alterations produced by SC do not produce degradation of temporal or spectral cues in speech or disruption of the perception of specific English phoneme segments. LEARNING OUTCOMES: As a result of this activity, the participant will be able to (1) describe simultaneous communication; (2) explain the role of simultaneous communication in communication with children who are deaf; (3) discuss methods of measuring speech intelligibility; and (4) specify the ability of listeners to perceive speech produced during simultaneous communication.

Effects of noise and filtering on the intelligibility of speech produced during simultaneous communication.

UNLABELLED: This study investigated the effects of noise and filtering on the intelligibility of speech produced during simultaneous communication (SC). Four normal hearing, experienced sign language users were recorded under SC and speech alone (SA) conditions speaking Boothroyd's forced-choice phonetic contrast material designed for measurement of speech intelligibility. Twenty-four normal hearing listeners audited the speech samples produced by the four speakers under the SC and SA conditions, three listeners in noise and three listeners in filtered listening conditions for each of the four speakers. Although results indicated longer sentence durations for SC than SA, the data showed no difference in the intelligibility of speech produced during SC versus speech produced during SA under either the noise or filtered listening condition, nor any difference in pattern of phonetic contrast recognition errors between the SA and SC speech samples in either listening condition. This conclusion is consistent with previous research indicating that temporal alterations produced by SC do not produce degradation of temporal or spectral cues to speech intelligibility or disruption of the perception of specific English phoneme segments. LEARNING OUTCOMES: As a result of this activity, the participant will be able to (1) describe simultaneous communication; (2) explain the role of simultaneous communication in communication with children who are deaf; (3) discuss methods of measuring speech intelligibility under filtered and noise conditions; and (4) specify the ability of listeners to perceive speech produced during simultaneous communication under noise and filtered listening conditions.