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Τετάρτη 13 Νοεμβρίου 2019

Retrospective multicentric study of pituitary incidentalomas
Unfortunately one of the co-author’s first name and last name had been wrongly published. The correct version is Maria Susana Mallea Gil and not Maria Susana, and Mallea Gil as published. Moreover, there occured an error in the first and surname of corresponding author Dr. Patricia Fainstein-Day. First name of the author is ‘Patricia’ and surname is ‘Fainstein-Day’.

ACRODAT® and AcroVoice: an insight into a holistic approach to the management of acromegaly

Surgical resection of granular cell tumor of the sellar region: three indications

Abstract

Purpose

This case series evaluates the surgical management of granular cell tumor (GCT) of the sellar region. This rare entity presents a unique diagnostic and surgical challenge.

Methods

Institutional neuropathology databases at Brigham and Women’s Hospital and Massachusetts General Hospital were searched for cases with a tissue diagnosis of GCT, and with a location in the sellar region. Patient, treatment, tumor, and follow-up data were extracted.

Results

Three patients had a diagnosis of GCT of the sellar region occurring over an 18-year period. All three patients were followed postoperatively at our multidisciplinary pituitary center (median follow-up = 30 months; range 12–30 months). Hormonal disturbances, an incidental lesion requiring diagnosis, and neurological symptoms were indications for surgery in these patients. Two patients underwent a craniotomy and one underwent endoscopic transsphenoidal surgery. All three patients were free of tumor recurrence at last follow-up. In one case tested, positive thyroid transcription factor-1 (TTF-1) immunohistochemistry was observed.

Conclusion

GCT is generally a benign tumor of the sellar region. Surgical resection is the standard treatment, more recently with transsphenoidal surgery when indicated. Surgical resection results in optimal outcome for patients.

Prediction of recurrence and remission within 3 years in patients with Cushing disease after successful transnasal adenomectomy

Abstract

Background

Some laboratory and clinical features are associated with a probability of recurrence after transnasal adenomectomy for Cushing disease (CD). However, there is no consensus on a set of predictors. Rules for prediction of recurrence were not proposed earlier.

Aim

To develop prediction model of recurrence/remission after successful neurosurgical treatment for CD.

Methods

Retrospective single-site comparative study included 349 patients (52 men and 297 women) with a verified diagnosis of CD who underwent effective endoscopic transsphenoidal adenomectomy between 2007 and 2014. Clinical and laboratory parameters were evaluated. Laboratory tests were performed using immunochemiluminescent method. Time-to-event analysis and ROC-analysis were applied. Multivariate models were developed using logistic regression and artificial neural network (ANN).

Results

Postoperative cortisol and ACTH levels and their combinations cannot be used for prediction of recurrence. ANN for prediction of recurrence within 3 years after successful surgery was developed. Input variables are age, duration of the disease, MRI data on adenoma, morning postoperative levels of ACTH and cortisol, output variable is binary (recurrence/remission). Predictive value for remission is 93%, 95% CI [89%; 96%], and predictive value for recurrence is 85%, 95% CI [71%; 94%]. Web-calculator based on the model is developed and free for use.

Conclusion

Effective method for prediction of recurrence and long-term remission within 3 years after successful endoscopic transsphenoidal adenomectomy is proposed.

Outcomes of stereotactic radiosurgery and hypofractionated stereotactic radiotherapy for refractory Cushing’s disease

Abstract

Purpose

Hypofractionated stereotactic radiotherapy (HSRT) for refractory Cushing’s disease may offer a condensed treatment schedule for patients with large tumors abutting the optic chiasm unsuitable for stereotactic radiosurgery (SRS). To-date only four patients have been treated by HSRT in the published literature. We investigated the feasibility, toxicity, and efficacy of HSRT compared to SRS.

Methods

After approval, we retrospectively evaluated patients treated at our institution for refractory Cushing’s disease with SRS or HSRT. Study outcomes included biochemical control, time to biochemical control, local control, and late complications. Binary logistic regression and Cox proportional hazards regression evaluated predictors of outcomes.

Results

Patients treated with SRS (n = 9) and HSRT (n = 9) were enrolled with median follow-up of 3.4 years. Clinicopathologic details were balanced between the cohorts. Local control was 100% in both cohorts. Time to biochemical control was 6.6. and 9.5 months in the SRS and HSRT cohorts, respectively (p = 0.6258). Two patients in each cohort required salvage bilateral adrenalectomy. Late complications including secondary malignancy, radionecrosis, cranial nerve neuropathy, and optic pathway injury were minimal for either cohort.

Conclusions

HSRT is an appropriate treatment approach for refractory Cushing’s disease, particularly for patients with large tumors abutting the optic apparatus. Prospective studies are needed to validate these findings and identify factors suggesting optimal fractionation approaches.

Intrasellar symptomatic salivary gland: case series and literature review

Abstract

Purpose

Ectopic salivary glands have been found in both extracranial and intracranial locations, however, intrasellar symptomatic salivary gland is extremely rare and its clinical manifestation, radiological characteristics and outcome have not been systematically studied. Here we present a case series of intrasellar symptomatic salivary gland and perform a literature review to better characterize this disease.

Methods

We retrospectively reviewed the data of three patients with intrasellar symptomatic salivary gland from our institutional and other cases available in literatures. Information for sex, age at diagnosis, clinical symptoms, radiological features, treatment strategy and prognosis were recorded.

Results

A total of 11 cases (including our own) were identified. There were three men and eight women, with an average age at diagnosis of 28.3 years. The peak incidence was in the second and the third decade (72.7% of all cases). The most common symptom was headache (81.8% of all patients). About 63.6% patients had one or more abnormal hormone levels, and prolactin was likely the most vulnerable hormone. The radiological appearances of intrasellar salivary gland were various, and four cases mimicked pituitary adenoma radiologically. All patients underwent transsphenoidal surgery with no mortality.

Conclusion

Although intrasellar symptomatic salivary gland is rare, it should be considered in the differential diagnosis of intrasellar lesions. Preoperative diagnosis is challenging since it mimics pituitary neoplasm in clinical and radiological manifestations, and confirmation for this disease could only be conducted through pathological examination. Transsphenoidal surgical resection is the preferred therapy and the patient prognosis is usually good.

A tale of pituitary adenomas: to NET or not to NET

Predictors of hypopituitarism due to vasculotoxic snake bite with acute kidney injury

Abstract

Purpose

Hypopituitarism frequently develops following vasculotoxic snake bite complicated by acute kidney injury (AKI). Well defined prospective studies of prevalence of hypopituitarism and its predictors in vasculotoxic snake bites complicated by AKI are unavailable.

Methods

Fifty-one consecutive patients of AKI following vasculotoxic snake bite were evaluated for various clinical/biochemical parameters (including Free T4, TSH, Cortisol, ACTH, total testosterone, FSH, LH, prolactin, and IGF-1). Diabetes insipidus was evaluated in relevant cases. Twenty minutes whole blood clotting time (WBCT) at presentation was measured in all. MRI of hypothalamo-pituitary region was done at 3 months in subjects with hypopituitarism to rule out structural lesion.

Results

21.6% (11/51) patients developed hypopituitarism at baseline (within 7 days), 39.3% (13 /33) at 3 months developed hypopituitarism. Cortisol deficiency was the commonest abnormality. Subjects who developed hypopituitarism at baseline were younger compared to those without hypopituitarism (35.67 years vs. 46.59 years, p = 0.032) and required more sessions of hemodialysis (8 vs. 3, p = 0.041). Binary logistic regression confirmed that development of hypopituitarism could be predicted by increased number of sessions of hemodialysis (OR 1.51, p = 0.008) and 20 min WBCT (OR 1.2, p = 0.038).

Conclusion

Hypopituitarism is common following vasculotoxic snake bite in subjects who develop AKI requiring hemodialysis. Hypopituitarism can develop as early as 7 days following snake bite and should be evaluated for particularly in younger subjects, especially those requiring increasing number of sessions of hemodialysis and in subjects with abnormal 20 min WBCT at presentation.

Development of a novel patient-reported measure for acromegaly: the Acro-TSQ

Abstract

Purpose

Somatostatin analogs (SSAs) represent a mainstay of medical treatment for acromegaly, currently available as either intramuscular or deep subcutaneous injections. Patient-reported outcomes (PROs) are increasingly common as relevant outcomes in studies of acromegaly and its treatment, but there are no validated PRO measures available that focus on the disease burden and the impact of treatment, specifically designed for use in patients with acromegaly. We sought to develop a new and unique PRO measure, the Acromegaly Treatment Satisfaction Questionnaire (Acro-TSQ).

Methods

Concept elicitation (CE) interviews were conducted with acromegaly patients in the United States receiving SSA injections at a stable dose for ≥ 6 months. A questionnaire was drafted based on these interviews; combined CE and cognitive debriefing (CE/CD) interviews were then conducted to confirm the content, clarity, and relevance of the questionnaire.

Results

Nineteen subjects completed interviews [n = 9 CE, n = 10 CE/CD; n = 15 Lanreotide Depot/Autogel (Somatuline), n = 4 Octreotide LAR (Sandostatin LAR)]. Most subjects responded positively when asked about the effectiveness of their current treatment; however, breakthrough symptoms, injection site reactions, and side effects were commonly reported and had negative impacts on social and emotional well-being and daily activities. All 10 subjects involved in debriefing interviews found the questionnaire to be relevant, easy to complete, and found the response options to be clear. The resulting 26-item Acro-TSQ covers symptoms and symptom control, gastrointestinal side effects and their impact on daily activities, the emotional impact of treatment, convenience and ease of use, and overall satisfaction.

Conclusions

The Acro-TSQ is a novel PRO, focused on both disease burden and impact of treatment; it was found to be comprehensive, clear, and relevant for patients with acromegaly receiving injectable SSA treatment.

MGMT immunohistochemistry in pituitary tumors: controversies with clinical implications

Abstract

Introduction

Temozolomide (TMZ) is currently considered as a rational therapeutic option for patients with progressively aggressive pituitary adenomas and carcinomas not responding to conventional therapies. Administration of TMZ results in clinical response and improvement in survival of many of these patients depending upon the expression of the DNA repair enzyme O-6 methylguanine DNA transferase (MGMT). Low or negative MGMT immunoreactivity predicts responsiveness to TMZ therapy. Therefore, MGMT serves as a criterion to select candidate patients anticipating response to treatment.

Materials and Methods

The MGMT expression was investigated in 25 pituitary adenomas with Ki-67 labeling index more that 3% and p53 expression, using various antigen retrieval protocols. After direct application of the antibody, only one adenoma yielded positive for MGMT. However, after pretreatment of tissue sections with antigen retrieval protocols, another 3 adenomas, initially negative turned to positive.

Conclusions

These findings could explain lack of response to TMZ treatment in patients with false negative MGMT immunohistochemistry. Evaluation of tumor samples for MGMT expression should carefully be carried-out using the optimum immunohistochemical protocol to obtain consistent and reliable results that help to identify patients that could respond to TMZ therapy.

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