Neuromonitoring Using Neurosonography and Pupillometry in A Weaning and Early Neurorehabilitation Unit.

BACKGROUND AND PURPOSE: Long-term surveillance of intracranial pressure (ICP) in neurological/neurosurgical patients during ventilator weaning and early neurorehabilitation currently relies on clinical observation because neuroimaging is rarely readily available. In this prospective study, multimodal neurosonography and pupillometry are evaluated for follow-up monitoring. METHODS: Sonographic neuromonitoring was used to noninvasively examine patients' ICP during weaning and early neurorehabilitation. It allowed assessments of third ventricle width, possible midline shift, middle cerebral artery flow velocities, and bilateral optic nerve sheath diameters. Quantitative pupillometry was used to determine pupil size and reactivity. Other neuroimaging findings, spinal tap ICP measurements, and clinical follow-up data served as controls. RESULTS: Seventeen patients-11 suffering from intracranial hemorrhage, four from encephalopathies, and two from ischemic stroke-were examined for ICP changes by using neurosonography and pupillometry during a mean observation period of 21 days. In total, 354 of 980 analyses (36.1%) yielded pathological results. In 15 of 17 patients (88.2%), pathological values were found during follow-up without a clear clinical correlate. In two patients (11.8%), clinically relevant changes in ICP occurred and were identified using neurosonography. Abnormal pupillometry findings displayed a high predictive value for absent clinical improvement. CONCLUSION: Multimodal neurosonography may be a noninvasive means for long-term ICP assessment, whereas pupillometry may only detect rapid ICP changes during acute neurointensive care. The study also illustrates common pitfalls in neuromonitoring in general, with large numbers of pathological albeit nonsignificant findings. Additional controlled studies should validate the influence of detected subtle changes in ICP on neurological outcome.

Pathological Complete Response to Neoadjuvant Trastuzumab Is Dependent on HER2/CEP17 Ratio in HER2-Amplified Early Breast Cancer.

Purpose: To evaluate whether pathologic complete response (pCR) to neoadjuvant trastuzumab is dependent on the level of HER2 amplification.Experimental Design: 114 HER2-overexpressing early breast cancer patients who had received neoadjuvant trastuzumab were included in this study. Absolute HER2 and chromosome 17 centromere (CEP17) were measured by in situ hybridization analysis, and associations were examined between HER2/CEP17 ratio and tumor pCR status (commonly defined by ypT0 ypN0, ypT0/is ypN0, and ypT0/is).Results: In trastuzumab-treated patients, ypT0 ypN0 was achieved in 69.0% of patients with high-level amplification (HER2/CEP17 ratio > 6), but only in 30.4% of tumors with low-level amplification (ratio ≤ 6; P = 0.001). When pCR was defined by ypT0/is ypN0 or ypTis, 75.9% and 82.8% of tumors with high-level amplification had a complete response, whereas only 39.1%, and 38.3% with low-level amplification achieved pCR (P = 0.002 and P < 0.001, respectively). Logistic regression revealed that tumors with high-level amplification had a significantly higher probability achieving ypT0 ypN0 (OR, 5.08; 95% confidence interval, 1.86-13.90; P = 0.002) than tumors with low-level amplification, whereas no other clinicopathologic parameters were predictive of pCR. The association between high-level HER2 amplification and pCR was almost exclusively confined to hormone receptor (HR)-positive tumors (ypT0 ypN0: 62.5% vs. 24.0%, P = 0.014; ypT0/is ypN0: 75.0% vs. 28.0%, P = 0.005; and ypT0/is: 87.5% vs. 28.0%, P < 0.001), and was largely absent in HR-negative tumors.Conclusions: An HER2/CEP17 ratio of >6 in the pretherapeutic tumor biopsy is associated with a significantly higher pCR rate, particularly in HER2/HR copositive tumors, and can be used as a biomarker to predict response before neoadjuvant trastuzumab is initiated. Clin Cancer Res; 23(14); 3676-83. ©2017 AACR.

Adjuvant sequencing of tamoxifen and anastrozole is superior to tamoxifen alone in postmenopausal women with low proliferating breast cancer.

PURPOSE: To assess the predictive value of Ki67 expression in postmenopausal hormone receptor-positive early-breast cancer patients, who were either treated with adjuvant tamoxifen (TAM) alone or with TAM followed by anastrozole (ANA). EXPERIMENTAL DESIGN: Expression of Ki67 was determined centrally by immunohistochemistry on whole tissue sections of postmenopausal endocrine-responsive breast cancers from patients who had been enrolled in the prospectively randomized Austrian Breast and Colorectal Cancer Study Group Trial 8, and had received TAM for 5 years, or TAM for 2 years followed by ANA for 3 years. Ki67 expression was evaluated both as a continuous variable and dichotomized to low (≤10%) and high (>10%). Recurrence-free survival (RFS) and overall survival (OS) were analyzed using Cox models adjusted for clinical and pathologic parameters. RESULTS: Patients with a high Ki67 expression (394/1,587; 23%) had a significantly shorter RFS (adjusted HR for recurrence = 1.90, 95% CI: 1.37-2.64, P = 0.0001) and OS (adjusted HR for death = 1.78, 95% CI: 1.18-2.70, P = 0.006). In women with breast tumors expressing medium or high ER levels (n = 1,438), the interaction between Ki67 and adjuvant endocrine treatment was significant for RFS (P = 0.03). TAM followed by ANA was superior to TAM alone in patients with low Ki67 (adjusted HR = 0.53, 95% CI: 0.34-0.83, P = 0.005) but not in high Ki67 disease (adjusted HR = 1.18, 95% CI: 0.66-1.89, P = 0.68). CONCLUSIONS: Adjuvant sequencing of TAM and ANA is superior to TAM alone, particularly in postmenopausal women with medium or high ER expressing, low proliferating breast cancer.

Primary angiosarcoma of the ovary with prominent fibrosis of the ovarian stroma. Case report of an 81-year old patient.

Primary angiosarcoma of the ovary (AS) is a rare entity with only 31 reported cases. The majority are pure angiosarcomas, the remainder are associated either with teratomas or conventional epithelial tumors. More than 50% of ovarian AS are disseminated at the time of diagnosis, the minority is detected in stage I. The prognosis of ovarian angiosarcoma in general is poor. Most reports refer to younger individuals, aged from 7 to 46 years, and only 2 case reports could be found for patients older than 64 years. Here we present a very unusual case of angiosarcoma in a 81-year-old patient.

Lymphoepithelioma-like carcinoma of the vulva, an underrecognized entity? Case report with a single inguinal micrometastasis detected by sentinel node technique.

This report describes an unusual EBV-negative lymphoepithelioma-like carcinoma of the vulva in a 73-year-old patient. The lesion was localised at the right minor labium and was resected by partial vulvectomy. A synchronous sentinel lymph node biopsy revealed a single micrometastasis in the right inguinal region, which prompted local radiotherapy. Follow-up nine months later showed only slight vulvar atrophy, without signs of local recurrence or distant metastases.Although lymphoepithelioma-like carcinomas of the skin and the female genital tract are presumed to have a better prognosis than their counterparts in the upper aerodigestive tract, possibly due to earlier detection and therapy, this case documents their potential for early metastasis.

Preoperative CYFRA 21-1 and CEA as prognostic factors in patients with stage I non-small cell lung cancer: external validation of a prognostic score.

OBJECTIVE: To validate the prognostic value of preoperative levels of CYFRA 21-1, CEA and the corresponding tumor marker index (TMI) in patients with stage I non-small cell lung cancer (NSCLC). METHODS: Two hundred forty stage I NSCLC patients (80 in pT1 and 160 in pT2; 100 squamous cell carcinomas, 91 adenocarcinomas, 32 large-cell carcinomas, 17 with other histologies; 171 males and 69 females) who had complete resection (R0) between 1986 and 2004 were included in the analysis. CYFRA 21-1 and CEA were measured using the Elecsys system (Roche) and AxSym-System (Abbott), respectively. Univariate analysis was performed using the Kaplan-Meier method to identify potential associations between survival and age, gender, CYFRA 21-1, CEA and TMI. RESULTS: Overall 3- and 5-year survival rates were 74 and 64%, respectively. Male gender (p = 0.0009) and age >70 years (p = 0.0041) were associated with a worse prognosis; there were no differences between pT1 and pT2 nor between histological subtypes. Three-year survival was 72% for CYFRA 21-1 levels >3.3 ng/ml versus 75% for levels 6.7 ng/ml versus 75% for CEA 0.05). Corresponding 5-year survival rates were near 64% both for patients with CYFRA 21-1 values above and below the cutoff (3.3 ng/ml), and 49 and 66% for patients with values above and below the CEA cutoff (6.7 ng/ml), respectively (both p values >0.05). Overall survival did not vary in the different TMI risk groups (p = 0.73). CONCLUSIONS: In this cohort of early-stage NSCLC patients, male gender and age >70 years were associated with a worse outcome, but elevated levels of CEA and CYFRA 21-1, and TMI risk were not.