New perspectives for mitotane treatment of adrenocortical carcinoma.

Adrenocortical carcinoma (ACC) is an aggressive cancer characterized by poor survival. Apart from radical surgery, there is a limited range of therapeutic options and mitotane remains the cornerstone of medical treatment of ACC in either adjuvant or palliative settings. The aim of adjuvant mitotane therapy is to reduce the risk of ACC recurrence following surgical removal of the tumor. Use of mitotane in an adjuvant setting is off-label, but the recent guidelines endorsed by the European Society of Endocrinology (ESE) and the European Network for the Study of Adrenal Tumors (ENSAT) recommend it in ACC patients at high risk of recurrence. The palliative use of mitotane for treatment of advanced ACC aims at controlling tumor progression and, when present, hormone secretion. In this clinical setting, mitotane is used in association with chemotherapy to treat the more aggressive forms, while mitotane monotherapy is reserved for less progressive ACC. Many years after its introduction in clinical practice, there are still uncertainties surrounding the use of this old drug and the derived benefits. Moreover, physicians who use mitotane should recognize and manage the systemic effects of the drug that need a complex supporting therapy.

Adjuvant mitotane therapy is beneficial in non-metastatic adrenocortical carcinoma at high risk of recurrence.

Objective Many patients with adrenocortical carcinoma (ACC) suffer from tumor recurrence despite radical surgery. Evidence on the post-operative use of mitotane is controversial and no predictors of response are available. We aimed to assess whether adjuvant mitotane treatment may prolong survival in patients with non-metastatic ACC following complete resection and whether ACC patients at high risk of recurrence may benefit from treatment. Design and methods We retrospectively reviewed data from 152 non-metastatic ACC patients followed at the San Luigi Gonzaga Hospital: 100 patients were treated with adjuvant mitotane and 52 patients were left untreated following surgery. We assessed a number of potential predictive factors of recurrence and death. Mitotane effect was explored stratifying patients by staging (stage I-II vs stage III), hormone secretion (yes vs no) and Ki67 index. Results The non-treated group had a higher risk of recurrence (HR: 2.79, 95%CI: 1.58-4.91; P < 0.001) than mitotane-treated group, while overall survival was not significantly different between groups. Hormone secretion, elevated Weiss score and elevated Ki67 index confer a higher risk of both recurrence and death and stage III ACC of death. Adjuvant mitotane treatment reduced significantly the risk of death in patients with elevated Ki67 index (P = 0.005) and in patients with stage III ACC (P = 0.02). Conclusions Adjuvant mitotane may prolong recurrence-free survival in radically resected ACC patients with acceptable toxicity and may also prolong overall survival in a subgroup of ACC patients at high risk of recurrence.

18F-FDG PET/CT in the post-operative monitoring of patients with adrenocortical carcinoma.

CONTEXT: The role of (18)F-labeled 2-fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET)/computed tomography (CT) in the post-operative monitoring of patients with adrenocortical carcinoma (ACC) is still unclear. OBJECTIVE: To assess the accuracy of FDG PET/CT to diagnose ACC recurrence in a real world setting. DESIGN AND METHODS: Retrospective evaluation of data of 57 patients with presumed ACC recurrence at CT scan who underwent FDG PET/CT within a median time of 20 days. We compared the results of either FDG PET/CT or CT with a gold standard confirmation of recurrence (positive histopathology report of removed/biopsied lesions or radiological progression of target lesions at follow-up) to assess their diagnostic performance at different body sites to correctly categorize target lesions. We also assessed whether FDG PET/CT findings may be useful to inform the management strategy. RESULTS: In 48 patients with confirmed ACC recurrence, we found that FDG PET/CT had lower sensitivity than CT in diagnosing liver and lung recurrences of ACC. FDG PET/CT had higher specificity than CT in categorizing liver lesions. FDG PET/CT had a greater positive likelihood ratio than CT to identify liver and abdominal ACC recurrences. The management strategy was changed based on FDG PET/CT findings in 12 patients (21.1%). CONCLUSIONS: The greater sensitivity of CT may be partly expected due the specific inclusion criteria of the study; however, the greater specificity of FDG PET/CT was particularly useful in ruling out suspected ACC recurrences found by CT. Thus, use of FDG PET/CT as a second-line test in the post-operative surveillance of ACC patients following CT finding of a potential recurrence may have a significant impact on patient management.

Mitotane levels predict the outcome of patients with adrenocortical carcinoma treated adjuvantly following radical resection.

CONTEXT: Mitotane plasma concentrations ≥ 14 mg/l have been shown to predict tumor response and better survival in patients with advanced adrenocortical carcinoma (ACC). A correlation between mitotane concentrations and patient outcome has not been demonstrated in an adjuvant setting. OBJECTIVE: To compare recurrence-free survival (RFS) in patients who reached and maintained mitotane concentrations ≥ 1 4 mg/l vs patients who did not. DESIGN AND SETTING: Retrospective analysis at six referral European centers. PATIENTS: Patients with ACC who were radically resected between 1995 and 2009 and were treated adjuvantly with mitotane targeting concentrations of 14-20 mg/l. MAIN OUTCOME MEASURES: RFS (primary) and overall survival (secondary). RESULTS: Of the 122 patients included, 63 patients (52%) reached and maintained during a median follow-up of 36 months the target mitotane concentrations (group 1) and 59 patients (48%) did not (group 2). ACC recurrence was observed in 22 patients of group 1 (35%) and 36 patients in group 2 (61%). In multivariable analysis, the maintenance of target mitotane concentrations was associated with a significantly prolonged RFS (hazard ratio (HR) of recurrence: 0.418, 0.22-0.79; P=0.007), while the risk of death was not significantly altered (HR: 0.59, 0.26-1.34; P=0.20). Grades 3-4 toxicity was observed in 11 patients (9%) and was managed with temporary mitotane discontinuation. None of the patients discontinued mitotane definitively for toxicity. CONCLUSIONS: Mitotane concentrations ≥ 14 mg/l predict response to adjuvant treatment being associated with a prolonged RFS. A monitored adjuvant mitotane treatment may benefit patients after radical removal of ACC.

Effect of Diuron on aquatic bacteria in laboratory-scale wastewater treatment ponds with special reference to Aeromonas species studied by colony hybridization.

Six laboratory-scale wastewater treatment ponds were filled with sediment and water obtained from a reference pond (a wastewater treatment plant located in a rural environment at Montel-de-Gelat, Puy-de-Dôme, France). They were kept at 20 degrees C, with alternative light and dark periods (12 h-12 h), and fed with raw effluent supplied weekly. Three of them were treated with Diuron (dissolved in DMSO) at a final concentration 10 mg/l, while the other three received only DMSO. Physico-chemical parameters, total bacteria, cultivable bacteria, and Aeromonas spp. were measured periodically until 41 days after the Diuron contamination. Total bacteria were treated with 4,6-diamidino 2-phenylindole (DAPI) and counted by epifluoroscence microscopy. The cultivable bacteria were quantified on plate count agar medium and Aeromonas spp. using colony hybridization. In the contaminated pilots, biochemical oxygen demand (BOD5), chemical oxygen demand (COD), suspended solids (SS), volatile suspended solids (VSS), ammonium, phosphorus, and bacteria increased, but dissolved oxygen decreased. The abundance of total bacteria, cultivable bacteria (multiplied by 30), and Aeromonas spp. increased for two weeks after Diuron introduction, reverting to initial values three weeks later. The percentage of cultivable bacteria relative to total bacteria was 0.2% in controls and 1.2% in treated pilots, while the percentage of Aeromonas spp. relative to cultivable bacteria decreased from 6-10% to 2%. Our results suggest that Diuron, which acts on the photosystem II of phototrophs, supports the development of cultivable bacteria through new carbon sources derived from the decomposition of photosynthetic micro-organisms, but does not specifically support Aeromonas spp.

Iatrogenic pneumocephalus in a man with undifferentiated nasopharyngeal carcinoma. A case report.

A case of pneumocephalus in a 45-year-old male with undifferentiated rhinopharyngeal carcinoma is described. The patient was initially subjected to radiotherapy and then to transmaxillary resection and a second course of stereotactic radiotherapy for recurrent disease. Lastly, the patient was treated with chemotherapy because of local-regional disease progression. After two cycles of cisplatin, adriablastine and bleomycin, the patient suddenly entered in coma. Cerebral CT scan evidenced the presence of air in the frontal and lateral cornua, in the subarachnoid space of the base cisternae extending to the 7th cervical vertebra. After 8 months of a clinical stationary condition, the patient died. The various treatments used are critically reviewed, and modern therapeutic approaches for the neoplasm and the toxicity involved are discussed. We conclude that in nasopharyngeal carcinoma, for patients who relapse after radiotherapy, successive local-regional therapies (surgery, re-irradiation) should be carefully evaluated to avoid demolishing treatments, which are burdened with severe side effects that might influence the quality of life with only slight improvement of overall survival. Furthermore, the presence of persistant aqueous rhinorrhea in these patients should be carefully evaluated, because it could be an early symptom of a cerebrospinal fluid leak.

Lymphocytic gastritis: a positive relationship with celiac disease.

Lymphocytic gastritis is characterized by lymphocytic infiltration of the surface and pit epithelium. Its cause has not been established, but an association with Helicobacter pylori infection or celiac disease has been suggested. We evaluated the histologic features of both gastric and duodenal biopsy specimens from 245 consecutive children and adolescents, and found chronic gastritis in 60 children and celiac disease in 25. Chronic gastritis was associated with H. pylori infection in 36 children and with celiac disease in 15. Lymphocytic gastritis was found in nine children with celiac disease. Children with lymphocytic gastritis had a mean of 40.64 lymphocytes per 100 epithelial cells, compared with a mean of 3.92 lymphocytes per 100 epithelial cells in children with H. pylori-associated gastritis and 5.15 lymphocytes in normal control subjects. Immunohistochemical studies showed that the intraepithelial lymphocytes in lymphocytic gastritis were T cells. No child with lymphocytic gastritis had serologic evidence of past H. pylori infection. We conclude that lymphocytic gastritis in children is associated with celiac disease. Dyspeptic symptoms are frequent; the endoscopic appearance is not characteristic.

[Biliary ileus: review of the literature and presentation of 7 cases]. / Ileo biliare: revisione della letteratura e presentazione di 7 casi.

The authors report 7 cases of gallstone ileus out of 452 intestinal obstructions corresponding to an incidence of 0.04%. The late references on the subject show that gallstone ileus is an unusual condition which gives rise to surgical approach problems and operating mortality since it is a typical seniors' disease. Some Authors support the "one stage" repair for cholecystoduodenal fistula and gallstone ileus, whereas others suggest firstly to resolve the gallstone ileus with the enterolithotomy and then to perform the operation for gallstone disease. The authors treated six cases with the enterolithotomy and one case with the "one stage" procedure, both the treatments were successful as all the patients survived even if affected by easily controlled complications.