Hepatospecific MR contrast agent uptake on hepatobiliary phase can be used as a biomarker of marked ß-catenin activation in hepatocellular adenoma.

OBJECTIVES: To assess the value of hepatospecific MR contrast agent uptake on hepatobiliary phase (HBP) images to detect marked activation of the ß-catenin pathway in hepatocellular adenomas (HCAs). METHODS: This multicentric retrospective IRB-approved study included all patients with a pathologically proven HCA who underwent gadobenate dimeglumine-enhanced liver MRI with HBP. Tumor signal intensity on HBP was first assessed visually, and lesions were classified into three distinct groups-hypointense, isointense, or hyperintense-according to the relative signal intensity to liver. Uptake was then quantified using the lesion-to-liver contrast enhancement ratio (LLCER). Finally, the accuracy of HBP analysis in depicting marked ß-catenin activation in HCA was evaluated. RESULTS: A total of 124 HCAs were analyzed including 12 with marked ß-catenin activation (HCA B+). Visual analysis classified 94/124 (76%), 12/124 (10%), and 18/124 (14%) HCAs as being hypointense, isointense, and hyperintense on HBP, respectively. Of these, 1/94 (1%), 3/12 (25%), and 8/18 (44%) were HCA B+, respectively (p < 0.001). The LLCER of HCA B+ was higher than that of HCA without marked ß-catenin activation in the entire cohort (means 4.9 ± 11.8% vs. - 19.8 ± 11.4%, respectively, p < 0.001). A positive LLCER, i.e., LLCER ≥ 0%, had 75% (95% CI 43-95%) sensitivity and 97% (95% CI 92-99%) specificity, with a LR+ of 28 (95% CI 8.8-89.6) for the diagnosis of HCA B+. CONCLUSIONS: Hepatospecific contrast uptake on hepatobiliary phase is strongly associated with marked activation of the ß-catenin pathway in hepatocellular adenoma, and its use might improve hepatocellular adenoma subtyping on MRI. KEY POINTS: • Tumor uptake on hepatobiliary phase in both the visual and quantitative analyses had a specificity higher than 90% for the detection of marked ß-catenin activation in hepatocellular adenoma. • However, the sensitivity of visual analysis alone is inferior to that of LLCER quantification on HBP due to the high number of HCAs with signal hyperintensity on HBP, especially those developed on underlying liver steatosis.

Neoadjuvant endocrine therapy with or without palbociclib in low-risk patients: a phase III randomized double-blind SAFIA trial.

BACKGROUND: The most prevalent subtype of breast cancer (BC) is luminal hormonal-positive breast cancer. The neoadjuvant chemotherapy regimens have side effects, emphasizing the need to identify new startegies. OBJECTIVE: Analyze the complete pathologic response (pCR) rate and overall response in a low-risk hormone-positive subset of patients receiving neoadjuvant hormone treatment (NAHT) with or without Palbociclib (a CDK4/CDK6 inhibitor) to boost NAHT effectiveness. MATERIALS AND METHODS: Based on the upfront 21-gene Oncotype DX or low-risk Breast Recurrence Score assay (RS™), the SAFIA trial is designed as a prospective multicenter international, double-blind neoadjuvant phase-III trial that selects operable with luminal BC patients that are HER2-negative for the induction hormonal therapy with Fulvestrant 500 mg ± Goserelin (F/G) followed by randomization of responding patients to palbociclib versus placebo. The pCR rate served as the study's main outcome, while the secondary endpoint was a clinical benefit. RESULTS: Of the 354 patients enrolled, 253 initially responded and were randomized to either F/G fulvestrant with palbociclib or placebo. Two hundred twenty-nine were eligible for the evaluation of the pathologic response. No statistically significant changes were observed in the pCR rates for the patients treated with the F/G therapy with placebo or palbociclib (7% versus 2%, respectively) per the Chevallier classification (Class1 + Class2) (p = 0.1464) and 3% versus 10% assessed per Sataloff Classification (TA, NA/NB) (p = 0.3108). Palbociclib did not increase the rate of complete pathological response. CONCLUSION: Neoadjuvant hormonal therapy is feasible in a selected population with a low RS score of < 31 CLINICAL TRIAL: NCT03447132.

Time dependent changes in aortic tissue during cold storage in physiological solution.

BACKGROUND: Stored vascular tissues are employed in biomedical research for studies in imaging, in biomechanics, and/or in assessing vessel diseases. In the present study, the stability of aortic tissue in phosphate buffer saline (PBS) at 4°C was monitored over a course of 10 days as determined by the rate of glucose permeation measured by optical coherence tomography (OCT) and validated by histology. METHODS AND RESULTS: The initial mean permeability through fresh porcine aorta was (2.32 ± 0.46)× 10(-5)cm/s (n=5); after maintaining the tissue at 4°C for 10 days, the mean rate was (7.37 ± 0.41)× 10(-5)cm/s (n=4), an increase of nearly 300%. A z-test verified that a significant change in the permeability rate (p<0.05) had occurred after 4 days of 4°C storage. Histology was used to quantify changes in tissue pore area. The increase in average pore area paralleled the increase in permeability rate over 10 days. CONCLUSIONS: These results suggest that (1) the structural integrity of aortic tissue at 4°C is retained for at least the first three days after resection and (2) OCT is a powerful technology well suited for evaluating tissue structural integrity over time. GENERAL SIGNIFICANCE: Functional OCT imaging provides for a noninvasive and quantitative technique in determining the structural integrity of aortic tissue stored at 4°C. This modality may be used for assessing the efficacy of other preservation techniques.

Permeation of human plasma lipoproteins in human carotid endarterectomy tissues: measurement by optical coherence tomography.

Atherosclerosis is an inflammatory process occurring in arterial tissue, involving the subintimal accumulation of LDL. Measurement of the rate at which LDL and other lipoproteins, such as HDL and VLDL, enter and exit the tissue can provide insight into the mechanisms involved in the development of atherosclerotic lesions. Permeation of VLDL, LDL, HDL, and glucose was measured for both normal and atherosclerotic human carotid endarterectomy tissues (CEA) at 20°C and 37°C using optical coherence tomography (OCT). The rates for LDL permeation through normal CEA tissue were (3.16 ± 0.37) × 10(-5) cm/s at 20°C and (4.77 ± 0.48) × 10(-5) cm/s at 37°C, significantly greater (P < 0.05) than the rates for atherosclerotic CEA tissue at these temperatures [(1.97 ± 0.34) × 10(-5) cm/s at 20°C and (2.01 ± 0.23) × 10(-5) cm/s at 37°C]. This study effectively used OCT to measure the rates at which naturally occurring lipoproteins enter both normal and diseased carotid intimal tissue.

Prediction of overall survival in patients with hepatocellular carcinoma treated with Y-90 radioembolization by imaging response criteria.

PURPOSE: To evaluate the potential of imaging criteria in predicting overall survival of patients with hepatocellular carcinoma (HCC) after a first transcatheter arterial yttrium-90 radioembolization (TARE) MATERIALS AND METHODS: From October 2013 to July 2017, 37 patients with HCC were retrospectively included. There were 34 men and 3 women with a mean age of 60.5±10.2 (SD) years (range: 32.7-78.9 years). Twenty-five patients (68%) were Barcelona Clinic Liver Cancer (BCLC) C and 12 (32%) were BCLC B. Twenty-four primary index tumors (65%) were>5cm. Three radiologists evaluated tumor response on pre- and 4-7 months post-TARE magnetic resonance imaging or computed tomography examinations, using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, modified RECIST (mRECIST), European Association for Study of the Liver (EASL), volumetric RECIST (vRECIST), quantitative EASL (qEASL) and the Liver Imaging Reporting and Data System treatment response algorithm. Kaplan-Meier survival curves were used to compare responders and non-responders for each criterion. Univariate and multivariate Cox proportional hazard ratio (HR) analysis were used to identify covariates associated with overall survival. Fleiss kappa test was used to assess interobserver agreement. RESULTS: At multivariate analysis, RECIST 1.1 (HR: 0.26; 95% confidence interval [95% CI]: 0.09-0.75; P=0.01), mRECIST (HR: 0.22; 95% CI: 0.08-0.59; P=0.003), EASL (HR: 0.22; 95% CI: 0.07-0.63; P=0.005), and qEASL (HR: 0.30; 95% CI: 0.12-0.80; P=0.02) showed a significant difference in overall survival between responders and nonresponders. RECIST 1.1 had the highest interobserver reproducibility. CONCLUSION: RECIST and mRECIST seem to be the best compromise between reproducibility and ability to predict overall survival in patients with HCC treated with TARE.

[Value of US imaging following mastectomy]. / Intérêt de l'échographie systématique du site de mastectomie.

PURPOSE: To assess the value of US of the mastectomy site at the time of follow-up of the contralateral residual breast. MATERIALS AND METHODS: Over a 5 year period, 251 patients with previous mastectomy underwent 505 unilateral mammographies with US of the mastectomy site. The time delay between imaging and mastectomy ranged between 1-15 years, with a mean of 7.5 years. Lesions at the mastectomy site were classified as follows: BIRADS 2 for a cyst or prominent edema, BIRADS 3 for a lymph node with preserved fatty hilum or mildly echogenic cyst, BIRADS 4 for well-defined hypoechoic lesions, and BIRADS 5 for ill-defined lesions. RESULTS: None of the lesions classified as BIRADS 1, 2 or 3 was malignant. Eleven lesions were classified as BIRADS 4: 3 benign lesions, 7 malignant lesions, and 1 non-verified lesion. No lesion was classified as BIRADS 5. CONCLUSION: Systematic US evaluation of the mastectomy site appears warranted since only 1 of 7 malignant lesions was clinically palpable prior to US whereas all were retrospectively palpable after US.

Lateralization index but not contralateral suppression at adrenal vein sampling predicts improvement in blood pressure after adrenalectomy for primary aldosteronism.

Adrenal vein sampling (AVS) is essential in differentiating unilateral from bilateral sources of aldosterone excess in primary aldosteronism (PA). However, its ability to predict blood pressure (BP) improvement after adrenalectomy has not been well studied. This is a retrospective observational study of 119 patients who underwent AVS by sequential technique followed by adrenalectomy for PA at the Hospital of the University of Pennsylvania from 1997 to 2015. Median age was 52 years (interquartile range 44-59), 67% were male and median duration of hypertension was 10 (interquartile range 6-20) years. A total of 76% and 90% of patients experienced BP improvement at 0-6 months or at any time point after surgery, respectively. Lateralization index (LI) >8, but not the presence of contralateral suppression, was significantly associated with BP improvement after surgery by multivariate logistic regression analysis adjusted for potential confounders (odds ratio (95% confidence interval): 17.1 (1.7-171.6) and 6.39 (0.06-641.8), respectively). A prediction score was created by covariates that was significantly associated with BP improvement in logistic regression analysis (duration of hypertension, body mass index, preoperative systolic BP and number of antihypertensive medications). Receiver-operating characteristic curve analyses showed that the addition of LI >8 to the score increased its ability to predict BP improvement (area under the curve 0.73-0.80). In conclusion, LI is useful in predicting improvement in BP after adrenalectomy for PA. The results of this study suggest that patients with long-standing severe hypertension may still benefit from surgery if LI >8.

Bilateral Choroidal Metastases from Prostate Cancer revealed in a patient under Abiraterone - Fourteen years after diagnosis.

Choroidal metastasis from prostate cancer is very rare and usually presents late during the disease. Since 2010, many new drugs were approved in the treatment of castrationresistant prostate cancer, including Abiraterone acetate. We report a case of bilateral choroidal metastases from prostate cancer 3 months after the initiation of Abiraterone. Abiraterone was not efficient in controlling the progression of the disease in this case, especially the choroidal metastasis. More case reports are essential in order to evaluate the role of Abiraterone in controlling choroidal metastases from prostate adenocarcinoma.

Long-term survivors after salvage high dose chemotherapy with bone marrow rescue in refractory germ cell cancer.

Between April 1984 and May 1985, 17 heavily pretreated patients with relapsing or refractory germ cell tumours were treated with cisplatin 40 mg/m2/day, days 1-5; etoposide 350 mg/m2/day, days 1-5; cyclophosphamide 1600 mg/m2/day, days 2-5 and autologous bone marrow transplantation on day 8 as consolidation of conventional salvage chemotherapy. None of the 11 refractory patients and 4 of the 6 responders to prior salvage treatment are long-term survivors at 68, 72, 74 and 74 months. Mean aplasia duration was 17 days and there were 7 documented episodes of septicaemia in 17 febrile patients. 1 patient died of treatment. Among the 4 survivors, 2 patients have a sustained grade II invalidating neuropathy. We conclude that this regimen is not recommended as salvage therapy in refractory patients but may be a useful consolidation treatment in patients responding to conventional salvage chemotherapy.

Phase II trial of combination chemotherapy with dacarbazine, cyclophosphamide, cisplatin, doxorubicin, and vindesine (DECAV) in advanced renal cell cancer.

Eighteen patients with advanced renal cell cancer were evaluated for objective response to a combination chemotherapy regimen twenty-eight-day (d) cycles, with dacarbazine (200 mg/sq m/d, d1,2,3); cyclophosphamide (400 mg/sq m/d, d1); cisplatin (100 mg/sq m/d, d1); doxorubicin (50 mg/sq m/d, d1); vindesine (1.5 mg/sq m/d, d1,2) (DECAV). One response in 16 patients was observed (6.25%; 95% confidence limits are 0-30%). No major toxicity occurred. An important point is that the only complete remission was observed in a patient with sarcomatoid cell renal cancer. At this dose with this schedule this combination regimen appears to have no activity in renal cell carcinoma.

Chemotherapy in metastatic nonanaplastic thyroid cancer: experience at the Institut Gustave-Roussy.

Forty-nine patients with metastatic nonanaplastic thyroid carcinoma were treated over a 10-year period. Five successive chemotherapeutic protocols were used: a combination of doxorubicin, etoposide, 5-fluorouracil and cyclophosphamide; elliptinium acetate; doxorubicin; cisplatin; and the combination of doxorubicin and cisplatin. Results obtained with the different protocols were very disappointing, with only two objective responses (3%). Phase II trials with new chemotherapeutic agents are warranted in selected cases of nonanaplastic metastatic thyroid carcinoma.

[Hypothalamo-hypophyseal and gastric metastasis of a breast neoplasm. Clinical case and a review of the literature]. / Métastases hypothalamo-hypophysaire et gastrique d'un cancer du sein. Cas clinique et revue de la littérature.

The authors report the case of a young woman with advanced breast cancer who developed diabetes insipidus due to pituitary involvement and also gastric metastases. This patient had a normal brain CT scan. Gastric metastases were diagnosed when she was operated for a perforated gastric ulcer. Although very rare, and even if the brain CT scan is normal, pituitary metastases should be diagnosed in the presence of suggestive clinical symptoms. Abdominal pain also warrants investigation in these patients in an early attempt to document any possible gastric metastases.

A phase II trial of early intensive chemotherapy with autologous bone marrow transplantation in the treatment of poor prognosis non seminomatous germ cell tumors.

Twenty-eight patients with poor prognosis, advanced metastatic non seminomatous germ cell tumors (NSGCT) were treated with early high dose chemotherapy and autologous bone marrow transplantation (ABMT) rescue. The primary tumor was testicular in 19 patients and extragonadal in nine patients. For 19 patients with a testicular primary, the median probability of complete remission (CR) was 0.05 according to our prognostic mathematical model based on pretreatment levels of serum HCG and AFP. The same prognostic model was used for extragonadal primaries. Treatment consisted of two cycles of a modified double dose of cisplatin, vinblastine, bleomycin, VP-16 regimen (mPVeBV) followed by a high dose cisplatin-etoposide-cyclophosphamide regimen (PEC) followed by ABMT. Of the 28 patients, 17 (61%) achieved CR, one of which was surgical CR (sCR), five died of rapidly progressive disease early during the first cycle of mPVeBV, two had treatment-related deaths, three did not respond and one patient refused treatment. Of the 17 patients initially in CR, three relapsed after 4, 4 and 7 months respectively and have subsequently died. Two other patients died while still in CR: one committed suicide and one died of an infectious complication due to transfusion-related AIDS. Twelve patients are alive in CR after a median follow-up of 66 months (range 7-72 months). The non parametric 3-year survival rate is 40%. To demonstrate the effect of intensive chemotherapy with ABMT, a randomized multicenter French study was set up to evaluate the PVeBV regimen with or without high dose treatment and ABMT in poor risk NSGCT patients.

[Chemotherapeutic intensification in germ cell tumors]. / Intensification chimiothérapique dans les tumeurs germinales.

Chemotherapy has dramatically improved the prognosis of non-seminomatous germ cell tumors (NSGCT). However, some patients relapse and others are refractory to first line chemotherapy. We studied a salvage chemotherapeutic regimen with etoposide 75 gm/m2/day, and cisplatin 40 mg/m2/day, days 1-5 and Ifosfamide 3 g/m2/day, days 1 and 2 (VIhP regimen) in 32 patients. We observed 8 complete remissions with 4 long-term NED patients. Hematological, neurological and renal complications were frequent. In 16 other cases, a protocol using high dose chemotherapy, followed by autologous bone marrow rescue was studied. We observed 8 complete remissions with 4 long-term NED patients. These observations support a dose/effect relationship. A French randomized trial testing high dose chemotherapy, followed in some cases by an autologous marrow graft in poor risk advanced NSGCT, has recently been activated.

Ifosfamide/mesna related encephalopathy: a case report with a possible role of phenobarbital in enhancing neurotoxicity.

A case of reversible encephalopathy after one dose of ifosfamide/mesna in an epileptic 15-year-old girl is reported. No other pathology could be responsible for the symptoms. An epilepsy or a toxicity induced by vincristine were discussed. Nevertheless, the possible role of phenobarbital, known to induce hepatic microsomal activity, seems the more probable mechanism.

[A phase III trial comparing the antiemetic activity of tetracosactide with dexamethasone in combination with metoclopramide, diphenhydramine and clorazepate during chemotherapy including cisplatin]. / Essai phase III comparant l'activité anti-émétique du tétracosactide à la dexaméthasone employés en association avec le metoclopramide, la diphénhydramine et le clorazépate au cours de chimiothérapies comportant du cisplatine.

In order to compare the safety and the antiemetic effectiveness of tetracosactide (TCS) or beta 1,24 ACTH with those of dexamethasone (DXM) as an adjunct to high-dose metoclopramide, diphenhydramine and clorazepate, 33 patients receiving cisplatin based cancer chemotherapy were enrolled in a double-blind cross-over clinical trial. TCS and DXM were given intravenously, respectively at a dose of 2 mg and 20 mg, and concurrently to the cisplatin infusion. No statistically significant difference was noted between the two drugs with regard to efficacy or side effects. We conclude that TCS can serve as a substitute for DXM in combination antiemetic regimens for management of cisplatin-induced nausea and vomiting.

[Value of high-dose chemotherapy followed by bone marrow autograft in non-seminomatous germinal tumor with poor prognosis. Results of the combination of cisplatinum, etoposide and cyclophosphamide (PEC protocol)]. / Intérêt de la chimiothérapie à haute dose suivie d'autogreffe de moelle osseuse dans les tumeurs germinales non séminomateuses de mauvais pronostic. Résultats de l'association cisplatinum, étoposide et cyclophosphamide (protocole PEC).

In recent years, the prognosis of non-seminomatous germ-cell tumors has been greatly improved by the use of novel chemotherapeutic regimens including platinum derivatives. However, the prognosis remains poor for a certain proportion of these patients. We have therefore developed an intensive chemotherapy protocol (PEC) followed by bone marrow autografting: cisplatin (40 mg/m2/day x 5 d), etoposide (350 mg/m2/day x 5 d), cyclophosphamide (1,600 mg/m2/day x 4 d). Forty-four poor-prognosis patients were thus treated. The results can be stratified into 3 categories, as follows: I: 12 refractory patients: 3 CR, 6 PR, 2 failures, 1 unevaluable. Median survival was short (7 months, range 2-16 months); II: 6 patients with sensitive relapse: 5 CR, 1 unevaluable. Four patients remained in CR at 42, 45, 46 and 48 months; III: 26 patients who received PEC as consolidation therapy in the first CR-PR after courses of conventional chemotherapy and who were selected at the time of diagnosis on the basis of factors of poor prognosis: 16 CR, 3 PR, 7 unevaluable. Two-year disease-free survival (Kaplan-Meier) is 60%. The median duration of neutropenia (less than 0.5 x 10(9)/l) was 15 d (range 6-37) and that of thrombocytopenia (less than 20 x 10(9)/l), 13 d (range 3-32). The most significant non-hematologic toxicity was of the gastrointestinal tract; in particular severe mucositis. Four iatrogenic deaths occurred (2 candidiasis, 1 aspergillosis and 1 hemorrhage). Pharmacokinetic studies were used to determine the optimum time for reinfusing the marrow and provided information on the mechanism of the mucositis. In conclusion, PEC protocol showed a high efficacy with 94% response rate (68.5% CR) among the 35 evaluable pts. Patients refractory to conventional treatment did not appear to benefit from this intensive chemotherapy. However, it appears that it may be useful for patients with relapses sensitive to salvage therapy. Encouraging results were obtained with the PEC protocol administered as early consolidation for patients with identifiable risk factors at diagnosis. A multicenter, randomized trial is currently underway in France to compare this approach with standard conventional chemotherapy.

[Gastric metastases of breast cancer]. / Métastases gastriques du cancer du sein.

Breast cancer is the most frequently encountered cancer in women and the first cause of death in the female population. Metastasis may occur ubiquitously depending on the histological type and the presence or absence of oestroprogesterone receptors. We report three cases with gastric metastasis. Signs of gastric involvement are often non-specific and should not be mistaken for simple side reactions to treatment. Hormone chemotherapy is indicated in most situations but surgery may be needed. It should be noted that gastrointestinal metastasis predominates in lobular breast cancers positive for progesterone receptors.