Adult “idiopathic” extrahepatic venous thrombosis

The etiology of extrahepatic venous obstruction (EHVO) is unknown in 50% of cases. Recently the presence of a latent myeloproliferative disorder has been reported in adults with idiopathic EHVO. We evaluated the course of these patients to establish if any putative latent myeloproliferative disorder influenced the clinical course compared to those with a known cause. Among 132 EHVO patients, 78 (59%) had a known etiology, 7 (5%) with an overt myeloproliferative disorder. The idiopathic group had 54 patients; 24 (13 men, 11 women) were diagnosed after 15 years of age, (median 38 years, range 17–70) with a median follow up of 96 months (19–372). Only 2 (8%) developed an overt myeloproliferative disorder. These 24 had a similar pattern of bleeding and onset of ascites as those with known cause. In EHVO failure to diagnose a latent myeloproliferative disorder does not influence the course of variceal bleeding, and thus has little prognostic significance.Supported by R Farini Foundation for Gastroenterology Research.     

Intrathecal chemotherapy in carcinomatous meningitis from breast cancer

Meningeal metastases occur in 2-3% of patients with breast cancer, leading to neurological morbidity and increased mortality. The criteria for treatment choice are controversial and intrathecal chemotherapy (ITC) has no documented role in the management of this disorder. We therefore evaluated the efficacy of an ITC regimen for patients presenting with carcinomatous meningitis from breast cancer. PATIENTS AND METHODS: Patients with meningeal carcinomatosis with or without concomitant parenchymal brain metastasis, were treated with repeated courses of intrathecal chemotherapy according to the following alternated weekly schedule: Day 1: Thiotepa 10 mg, methotrexate 15 mg, hydrocortisone 30 mg; Day 5: cytarabine (Ara-C) 70 mg, methotrexate 15 mg, hydrocortisone 30 mg. Folinic acid 15 mg was given orally, every six hours after methotrexate on days 2-3 and 6-7. RESULTS: Thirteen consecutive patients were treated. The median age was 45 (range 30-67) years. Eleven patients had performance status (PS) 2-3. Nine patients had other metastatic sites; synchronous parenchymal brain metastasis were present in 5 patients. Concomitant systemic chemotherapy was administered in 5 patients and external whole brain radiotherapy in 7 patients. With 12 evaluable patients we observed no responses or improvement in symptoms. Side-effects were minimal. CONCLUSION: In our series of patients, ITC failed to provide objective response or relief in clinical symptoms. Despite evidence reported in the literature indicating symptomatic improvement after ITC in a number of patients with leptomeningeal metastasis, the results of our study confirm the controversial role of ITC. New drugs and new modalities of treatment should be studied in order to efficiently control meningeal involvement of breast cancer.     

Long-term outcomes of grade I/II skull base chondrosarcoma: an insight into the role of surgery and upfront radiotherapy

Journal of Neuro-Oncology - To clarify the need for post-operative radiation treatment in skull base chondrosarcomas (SBCs). A retrospective analysis of patients with grade I or II SBC. Patients...     

Knowledge Translation at the Macro Level: Legal and Ethical Considerations

Macro-level legal and ethical issues play a significant role in the successful translation of knowledge into practice. The medicolegal milieu, in particular, can promote clinical inertia and stifle innovation. Embracing new clinical practice guidelines and best practice models has not protected physicians from superfluous torts; in some cases, emerging evidence has been used as the dagger of trial lawyers rather than the scalpel of physicians. Beyond the legal challenges are overarching justice issues that frame the broad goals of knowledge translation (KT) and technology diffusion. Optimal implementation of the latest evidence requires attention to be paid to the context of the candidate community and the key opinion leaders therein, characterized by the "8Ps" (public, patients, press, physicians, policy makers, private sector, payers, and public health). Ethical and equitable KT also accounts for the global burdens and benefits of implementing innovation such that disparities and gaps in health experienced by the least advantaged are prioritized. Researchers and thought leaders must attend to questions of fairness, economics, and legal risk when investigating ways to promote equity-oriented KT.     

Epidoxorubicin and docetaxel as first-line chemotherapy in patients with advanced breast cancer: a multicentric phase I-II study.

Background:The combination of anthracyclines and taxanes iscurrently considered the first choice chemotherapy in advanced breast cancer(ABC) and considerable emphasis has been placed on programs exploring thesafest and most efficient way to integrate these classes of drugs in both themetastatic and, more recently, the adjuvant setting.We report here the overall results of the combination of epidoxorubicin (E)90 mg/m² and docetaxel (D) 75 mg/m² as first-linechemotherapy in ABC. Patients and methods:A total of 70 patients were entered in theinitial dose-finding study (20 patients) and in the subsequent extended phaseII trial (50 patients). Overall 54% of patients had dominant visceraldisease and 57% had at least two metastatic sites. Adjuvantanthracyclines were allowed in the phase II part of the study based on thelack of cardiac toxicity observed in the phase I study at a median cumulativeE dose of 480 mg/m². A maximum of eight cycles of the combinationwas allowed, and cardiac function was monitored at baseline and after everysecond course by echocardiography. Results:Overall, the median number of cycles administered withthe combination was 4 (range 3–8). Neutropenia was confirmed to be themain haematological toxicity, with granulocyte colony-stimulating factor(G-CSF) support required in 44% of the cycles. Febrile neutropeniaoccurred in 12% of cycles of the combination but 52% of theepisodes could be managed on an outpatient basis with oral antibiotics.Overall, the median cumulative dose of E, including prior adjuvantanthracyclines, was 495 mg/m² (range 270–1020mg/m²). One patient who received adjuvant E together withradiotherapy to the left chest wall developed fully reversible clinical signsof cardiotoxicity and a significant decrease of LVEF to 35% after acumulative E dose of 870 mg/m², with four additional patients(6%) developing asymptomatic and transient decline of resting LVEF. Theoverall response rate (ORR) in 68 evaluable patients was 66%(95% confidence interval (95% CI): 54%–73%).A comparable antitumour activity of 71% was reported in the group ofpatients with a prior adjuvant chemotherapy with anthracyclines. After anoverall median follow-up time of 22 months (range 4–39+), the mediantime to progression (TTP) was 4.5 months and the median duration of responsewas 8 months (range 3–16). No pharmacokinetic (Pk) interaction could bedemonstrated between E and D when given simultaneously and sequentially witha one-hour interval. Conclusions:The combination of E and D in a multi-institutionalsetting is an active and safe regimen in poor- prognosis patients with ABC.New combinations and schedules are worth considering in an attempt to furtherimprove disease response and long-term control of the disease.     

Analysis for indole compounds in urine by high-performance liquid chromatography with fluorometric detection.

We describe a chromatographic system involving a high-performance chemically-bonded reverse-phase column and fluorescence detection for measurement of indoles in urine. We controlled retention and selectivity by optimizing the methanol content and pH of the mobile phase. Six reference indoles were separated in less than 20 min; three 5-hydroxyindoles were eluted in less than 7 min. About 5-15 ng of aqueous solutions of these compounds can be detected. The combination of selectivity (from use of the chromatographic column) and fluorescence detection permitted analysis for five of the six indoles after a single urine-deproteinization step.     

The dangers of the “Head Down” position in patients with untreated pituitary macroadenomas: case series and review of literature

Purpose

Cavernous sinus syndrome is a rare phenomenon, characterized by simultaneous neuropathies of cranial nerves III–VI. Various pathological processes have been reported as precipitating etiologies, including infection, inflammation, vascular lesions, and neoplasms.

Purpose

We report a unique case series of cavernous sinus syndrome attributable to prolonged Trendelenburg or prone positioning during non-cranial procedures and review the pertinent literature to enlighten on this rare but catastrophic phenomenon.

Methods

Retrospective case series.

Results

In the past year we encountered two patients who presented with acute cavernous sinus syndrome upon awakening from non-cranial operations. One patient underwent an extensive urologic resection of a bladder malignancy positioned in Trendelenburg for approximately 4 h. The second patient underwent a lumbar laminectomy and discectomy in prone position. Both patients were discovered to have infarcted large pituitary macroadenomas as the etiology of their acute ophthalmoplegias, and transnasal, transsphenoidal resection was performed acutely to decompress the cavernous sinus contents. Pathologic analysis of the resected specimens in each case confirmed necrotic, infarcted pituitary adenoma. Both patients made a complete recovery with no evidence of residual or recurrent tumor in short term follow-up.

Conclusion

We report a brief case series of acute cavernous sinus syndrome resulting from dependent positioning during non-cranial operations in patients with pituitary macroadenoma. Although rare, this highlights a potential danger of “head down” positioning in patients with intracranial pathology—particularly in or around the sella and cavernous sinus. Despite multiple cranial neuropathies upon presentation, both patients made complete recovery following surgical decompression of the cavernous sinuses.