Transcriptomic and clinical heterogeneity of metastatic disease timing within metastatic castration-sensitive prostate cancer.

BACKGROUND: Metastatic castration-sensitive prostate cancer (mCSPC) is commonly classified into high- and low-volume subgroups which have demonstrated differential biology, prognosis, and response to therapy. Timing of metastasis has similarly demonstrated differences in clinical outcomes; however, less is known about any underlying biologic differences between these disease states. Herein, we aim to compare transcriptomic differences between synchronous and metachronous mCSPC and identify any differential responses to therapy. PATIENTS AND METHODS: We performed an international multi-institutional retrospective review of men with mCSPC who completed RNA expression profiling evaluation of their primary tumor. Patients were stratified according to disease timing (synchronous versus metachronous). The primary endpoint was to identify differences in transcriptomic profiles between disease timing. The median transcriptomic scores between groups were compared with the Mann-Whitney U test. Secondary analyses included determining clinical and transcriptomic variables associated with overall survival (OS) from the time of metastasis. Survival analysis was carried out with the Kaplan-Meier method and multivariable Cox regression. RESULTS: A total of 252 patients were included with a median follow-up of 39.6 months. Patients with synchronous disease experienced worse 5-year OS (39% versus 79%; P < 0.01) and demonstrated lower median androgen receptor (AR) activity (11.78 versus 12.64; P < 0.01) and hallmark androgen response (HAR; 3.15 versus 3.32; P < 0.01). Multivariable Cox regression identified only high-volume disease [hazard ratio (HR) = 4.97, 95% confidence interval (CI) 2.71-9.10; P < 0.01] and HAR score (HR = 0.51, 95% CI 0.28-0.88; P = 0.02) significantly associated with OS. Finally, patients with synchronous (HR = 0.47, 95% CI 0.30-0.72; P < 0.01) but not metachronous (HR = 1.37, 95% CI 0.50-3.92; P = 0.56) disease were found to have better OS with AR and non-AR combination therapy as compared with monotherapy (P value for interaction = 0.05). CONCLUSIONS: We have demonstrated a potential biologic difference between metastatic timing of mCSPC. Specifically, for patients with low-volume disease, those with metachronous low-volume disease have a more hormone-dependent transcriptional profile and exhibit a better prognosis than synchronous low-volume disease.

Whole abdominopelvic radiotherapy in the palliative treatment of pseudomyxoma peritonei.

BACKGROUND: Pseudomyxoma peritonei (PMP) is a rare clinical syndrome characterized by mucinous peritoneal disease arising from disseminated peritoneal adenomucinosis. Primary treatment involves a combination of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC). There is no consensus on the proper treatment of recurrent PMP. In selected patients, repeated cytoreductive surgery with or without HIPEC might improve outcome. However, every repeated debulking procedure becomes less effective with increased morbidity. CASE REPORT: We present a case of a patient with intestinal obstruction caused by recurrent pseudomyxoma peritonei. We treated the patient with whole abdominopelvic radiotherapy (WAPRT) using intensity-modulated arc therapy (IMAT) to a total dose of 33 Gy, delivered in 22 daily fractions. The treatment was well tolerated and resulted in resolution of the obstruction for a period of 24 months. CONCLUSION: To the best of our knowledge, we present the first case report showing the possibility of resolving intestinal obstruction with WAPRT in a patient with recurrent PMP. It is our opinion that WAPRT delivered by IMAT, in analogy with ovarian cancer, should be considered as a palliative treatment option in managing patients with recurrent PMP especially in case of obstruction.

Intensity-modulated arc therapy with cisplatin as neo-adjuvant treatment for primary irresectable cervical cancer. Toxicity, tumour response and outcome.

PURPOSE: The goal of this work was to evaluate the feasibility and outcome of intensity-modulated arc therapy ± cisplatin (IMAT ± C) followed by hysterectomy for locally advanced cervical cancer. PATIENTS AND METHODS: A total of 30 patients were included in the study. The primary tumour and PET-positive lymph node(s) received a simultaneous integrated boost. Four weeks after IMAT ± C treatment, response was evaluated. Resection consisted of hysterectomy with or without lymphadenectomy. Tumour response, acute and late radiation toxicity, postoperative morbidity and outcome were evaluated. RESULTS: All hysterectomy specimens were macroscopically tumour-free with negative resection margins; pathological complete response was 40%. In 2 patients, one resected lymph node was positive. There was no excess in postoperative morbidity. Apart from two grade 3 hematologic toxicities, no grade 3 or 4 acute radiation toxicity was observed. No grade 3, 1 grade 4 (4%) intestinal, and 4 grade 3 (14%) urinary late toxicities were observed. The 2-year local and regional control rates were 96% and 100%, respectively. The 2-year distant control rate was 92%. Actuarial 2-year progression free survival rate was 89%. Actuarial 1- and 2-year overall survival rates were 96% and 91%, while 3-year overall survival was 84%. CONCLUSION: Surgery after IMAT ± C is feasible with low postoperative morbidity and radiation toxicity. Local, regional, distant control and survival rates are promising.

Tissue perfusion in pathologies of the pancreas: assessment using 128-slice computed tomography.

PURPOSE: Perfusion CT can provide information regarding blood perfusion and permeability in (tumor) tissues in a non-invasive manner. In this study, values of CT perfusion parameters in several pancreas pathologies were determined and compared to a control population. MATERIALS AND METHODS: Dynamic 128-slice perfusion CT was performed in patients admitted to the radiology department between June 2010 and March 2011. Included pathologies were pancreatic adenocarcinoma, acute and chronic pancreatitis, neuroendocrine tumors, and (pseudo)cystic lesions. Parametric mappings of blood flow, blood volume, and permeability surface area product were generated. RESULTS: Blood flow and blood volume were significantly lower in acute and chronic pancreatitis compared to the control group. In the center of adenocarcinoma tumors, low blood flow and blood volume was observed, gradually increasing toward the tumor rim; perfusion values in pancreatic parenchyma adjacent to the tumor were not significantly different from the control population. In neuroendocrine tumors, significantly increased perfusion values were observed. CONCLUSION: Compared to the control population, significant decreases in perfusion values were observed in all pancreatic pathologies under study, except in neuroendocrine tumors. Perfusion CT values can be used as an additional parameter to differentiate pancreatic pathologies.

Primary sinonasal mucosal melanoma: three different therapeutic approaches to inoperable local disease or recurrence and a review of the literature.

Sinonasal melanoma is an uncommon disease with a bad prognosis and a high local recurrence rate. The use of radiotherapy in such conditions remains controversial. A review of the literature is presented in an attempt to answer some of the questions regarding therapeutic options. Data on incidence, aetiology, pathology and prognosis are also provided. Case studies are reported of three patients with sinonasal melanoma referred to our department in a relatively short time period and needing radiotherapy as a single treatment modality, using a conformal three-dimensional treatment technique. One patient was also treated with temporary 1251 seeds, while another was treated using intensity modulation. Both intensity modulation and temporary 1251 seeds are feasible techniques, providing satisfactory dose distributions encompassing the tumour volume while sparing critical structures. Surgery remains the treatment of choice for sinonasal melanoma. Radiotherapy should be used postoperatively and is a good alternative in cases of inoperable disease. Adjacent critical structures limit the radiation dose to the tumour area, especially when high fraction doses are used. Therefore, beam intensity modulation and 1251 seeds can be used to increase the tumour dose without exceeding the radiation tolerance of the surrounding structures.

Fetal hearing.

The fetus can hear during the last trimester of pregnancy. Consistent responses to acoustic stimuli have been observed from 28 weeks onwards. Animal experiments as well as investigations in the human lead to the conclusion that sounds from outside the mother are attenuated, but rarely by more than 30 decibels; external conversations are audible. Only 30% of the phonetic information is available to the fetus, but intonation is almost perfectly transmitted to the amniotic sac. Evidence is accumulating that the mother's voice or different sound patterns from the same voice are learnt by the fetus. Thus there are indications that short-term auditory memory may be present by the end of pregnancy.

Longitudinal quantification of inflammation in the murine dextran sodium sulfate-induced colitis model using µPET/CT.

BACKGROUND: This study investigates whether deoxy-2-[18F]fluoro-d-glucose (FDG) micro-positron emission tomography (µPET)/computed tomography (CT) can serve as a tool for monitoring of the commonly used dextran sodium sulfate (DSS)-induced murine model of inflammatory bowel disease (IBD). METHODS: DSS-colitis was induced in Sv129 mice. In a first experiment, four animals were serially scanned with CT and FDG-µPET on days 0, 3, 7, 11, and 14. The ratio of the mean voxel count of the PET images in the colon and the brain was compared with the histological inflammation score and the colonic myeloperoxidase levels. A second experiment was performed to investigate whether FDG-µPET was able to detect differences in inflammation between two DSS-treated groups, one receiving placebo (n = 4) and one receiving dimethyloxalylglycine (DMOG) (n = 4), a compound that protects against DSS-induced colitis. RESULTS: The progression of the colonic/brain FDG-signal ratio (over days 0-14) agreed with the predicted histological inflammation score, obtained from a parallel DSS-experiment. Moreover, the quantification of normalized colonic FDG-activity at the final timepoint (day 14) showed an excellent correlation with both the MPO levels (Spearman's rho = 1) and the histological inflammation score (Spearman's rho = 0.949) of the scanned mice. The protective action of DMOG in DSS colitis was clearly demonstrated with FDG-µPET/CT (normalized colonic FDG-activity DMOG versus placebo: P < 0.05). CONCLUSIONS: FDG-µPET-CT is a feasible and reliable noninvasive method to monitor murine DSS-induced colitis. The implementation of this technique in this widely used IBD model opens a new window for pathophysiological research and high-throughput screening of potential therapeutic compounds in preclinical IBD research.

[Intra-amniotic transmission of the human voice]. / La transmission intra-amniotique des voix humaines.

New acoustic measurements in amniotic environment permit to specify the conditions of transmission of human voices: voices emerge, incompletely covered by a low background noise, but however higher pitched near the placenta. The recognition of phonemes in utero is rather weak, approximately 30 per cent and appreciably identical for all voices and different mode of emission. Therefore this type of recognition is likely to play a minor role: the voices are evenly toneless by lack of high-pitch, and there is no obvious superiority of the intelligibility of direct maternal voice. The recognition of vowels by their second forming, as well as the emergence (demonstrated with special microphones) of impulse noises with very high-pitch components and of synthetic speech, confirm the possibility of transmission of frequencies exceeding 1,500 Hz to the intra-amniotic environment. On the contrary, melody recognition is excellent: probably major role of this factor. The loudness of the maternal voice transmitted to the uterus exceeds markedly that of outside voices, and this voice is certainly accessible to the fetus, most of the time. The demonstration of the transmission to the amniotic fluid of noises and voices enables to consider the possibility of perception.