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Cancer Immunology, Immunotherapy : CII Jun 2021To summarize the clinical characteristics and immunological and genetic features of patients who developed autoimmune polyendocrine syndrome type II (APS-2) after...
OBJECTIVE
To summarize the clinical characteristics and immunological and genetic features of patients who developed autoimmune polyendocrine syndrome type II (APS-2) after treatment with immune checkpoint inhibitors (ICIs).
DESIGN AND METHODS
Several databases (MEDLINE/EMBASE/Cochrane) were searched for studies published between January 2000 and February 2020 involving patients with two or more endocrine disorders after ICI therapy.
RESULTS
Our final review included 22 articles comprising 23 patients (median age 56 years; 65.2% male patients). Of these patients, 60.9% received anti-programmed cell death 1 (PD-1) therapy, 17.4% received anti-programmed cell death ligand 1 (PD-L1) therapy, and 4.3% received anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) monotherapy. Patients underwent a median of four treatment cycles before the onset of the primary adverse event; the median time of onset was 8.5 weeks. Endocrine organs affected by ICI administration included the thyroid gland (18/23, 78.3%), pancreatic islets (17/23, 73.9%), pituitary gland (11/23, 47.8%), and adrenal gland (2/23, 8.7%). Related autoantibodies were detected in 65.2% of patients. In patients with diabetes, glutamic acid decarboxylase antibody was closely related to the development of diabetes ketoacidosis. The human leukocyte antigen genotype was reported in 34.8% (8/23) of patients, 5 (62.5%) of which had risk genotypes.
CONCLUSIONS
As a serious adverse event of ICI treatment, APS-2 is presented with abrupt initiation time and rapid development. Physicians should be aware of potential endocrine disorders and continue monitoring hormone status when treating cancer patients with ICIs.
Topics: Humans; Immune Checkpoint Inhibitors; Neoplasms; Polyendocrinopathies, Autoimmune; Prognosis
PubMed: 33200250
DOI: 10.1007/s00262-020-02699-1 -
PloS One 2020Childhood craniopharyngioma is a rare and slow growing brain tumour, often located in the sellar and suprasellar region. It commonly manifests with visual impairment,...
Childhood craniopharyngioma is a rare and slow growing brain tumour, often located in the sellar and suprasellar region. It commonly manifests with visual impairment, increased intracranial pressure and hypothalamic and/or pituitary deficiencies. Visual impairment in childhood adversely affects a child's daily functioning and quality of life. We systematically reviewed the literature to provide an extensive overview of the visual function in children with craniopharyngioma at diagnosis in order to estimate the diversity, magnitude and relevance of the problem of visual impairment. Of the 543 potentially relevant articles, 84 studies met our inclusion criteria. Visual impairment at diagnosis was reported in 1041 of 2071 children (50.3%), decreased visual acuity was reported in 546 of 1321 children (41.3%) and visual field defects were reported in 426 of 1111 children (38.3%). Other ophthalmological findings described were fundoscopic (32.5%) and orthoptic abnormalities (12.5%). Variations in ophthalmological testing methods and ophthalmological definitions precluded a meta-analysis. The results of this review confirm the importance of ophthalmological examination in children with craniopharyngioma at diagnosis in order to detect visual impairment and provide adequate support. Future studies should focus on long-term visual follow-up of childhood craniopharyngioma in response to different treatment strategies to provide insight in risks and ways to prevent further loss of vision.
Topics: Child; Craniopharyngioma; Humans; Pituitary Neoplasms; Risk; Vision, Ocular
PubMed: 33002047
DOI: 10.1371/journal.pone.0240016 -
BMC Neurology Aug 2020Perioperative cerebrospinal fluid (CSF) leakage is a major complication of pituitary adenomas transsphenoidal surgery. Lumbar drainage (LD) is a common method of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Perioperative cerebrospinal fluid (CSF) leakage is a major complication of pituitary adenomas transsphenoidal surgery. Lumbar drainage (LD) is a common method of treating CSF leakage. But whether intraoperative LD can prevent CSF leakage during the perioperative period of pituitary adenomas transsphenoidal surgery remains controversial. Clarity on the appropriate use of LD is needed.
METHODS
A systematic literature review was conducted in the PubMed, EMBASE, and Web of science databases. Articles were included when they compared intraoperative LD with intraoperative no-LD CSF leakage rates during pituitary adenomas transsphenoidal surgery.
RESULTS
Overall, 5 studies containing 678 cases met the inclusion criteria. When data were provided on intraoperative CSF leakage rates, the meta-analysis showed a significant difference in favor of intraoperative LD. When data were provided on postoperative CSF leakage rates, the meta-analysis also demonstrated a significant difference in favor of intraoperative LD.
CONCLUSIONS
Although the results of this meta-analysis suggest intraoperative LD can reduce the risk of CSF leakage during the perioperative period of pituitary adenomas transsphenoidal surgery, the available evidence is indefinite. To some extent the results suggest intraoperative LD's potential positive role. Further studies that include well-designed prospective, randomized controlled clinical trials are necessary for further verification.
Topics: Adenoma; Cerebrospinal Fluid Leak; Drainage; Humans; Intraoperative Care; Lumbosacral Region; Pituitary Gland; Pituitary Neoplasms; Postoperative Complications; Sphenoid Bone
PubMed: 32799821
DOI: 10.1186/s12883-020-01877-z -
Endocrine Nov 2020Recurrence after pituitary surgery in Cushing's disease (CD) is a common problem ranging from 5% (minimum) to 50% (maximum) after initially successful surgery,... (Review)
Review
PURPOSE
Recurrence after pituitary surgery in Cushing's disease (CD) is a common problem ranging from 5% (minimum) to 50% (maximum) after initially successful surgery, respectively. In this review, we give an overview of the current literature regarding prevalence, diagnosis, and therapeutic options of recurrent CD.
METHODS
We systematically screened the literature regarding recurrent and persistent Cushing's disease using the MESH term Cushing's disease and recurrence. Of 717 results in PubMed, all manuscripts in English and German published between 1980 and April 2020 were screened. Case reports, comments, publications focusing on pediatric CD or CD in veterinary disciplines or studies with very small sample size (patient number < 10) were excluded. Also, papers on CD in pregnancy were not included in this review.
RESULTS AND CONCLUSIONS
Because of the high incidence of recurrence in CD, annual clinical and biochemical follow-up is paramount. 50% of recurrences occur during the first 50 months after first surgery. In case of recurrence, treatment options include second surgery, pituitary radiation, targeted medical therapy to control hypercortisolism, and bilateral adrenalectomy. Success rates of all these treatment options vary between 25 (some of the medical therapy) and 100% (bilateral adrenalectomy). All treatment options have specific advantages, limitations, and side effects. Therefore, treatment decisions have to be individualized according to the specific needs of the patient.
Topics: ACTH-Secreting Pituitary Adenoma; Adrenalectomy; Adult; Child; Female; Humans; Neoplasm Recurrence, Local; Pituitary ACTH Hypersecretion; Pituitary Gland; Pregnancy; Recurrence; Treatment Outcome
PubMed: 32743767
DOI: 10.1007/s12020-020-02432-z -
Pituitary Aug 2020Surgery in patients with non-functioning pituitary macroadenomas (NFMA) is effective in ameliorating visual function. The urgency for decompression, and preferred timing...
Quality of care evaluation in non-functioning pituitary adenoma with chiasm compression: visual outcomes and timing of intervention clinical recommendations based on a systematic literature review and cohort study.
PURPOSE
Surgery in patients with non-functioning pituitary macroadenomas (NFMA) is effective in ameliorating visual function. The urgency for decompression, and preferred timing of surgery related to the preoperative severity of dysfunction is unknown.
METHODS
Systematic review for evidence to provide clinical guidance for timing of surgical decompression of the optic chiasm, and a cohort study of 30 NFMA patients, in whom mean deviation (MD), and severity of visual dysfunction was assessed.
RESULTS
Systematic review 44 studies were included with a total of 4789 patients. Postoperatively, visual field defects improved in 87.0% of patients, stabilized in 12.8% and worsened in 1.0%. Specific protocols regarding timing of surgery were not reported. Only seven studies (16.7%) reported on either the duration of visual symptoms, or diagnostic, or treatment delay. Cohort study 30 NFMA patients (50% female, 60 eyes, mean age 58.5 ± 14.8 years), had a median MD of - 5.3 decibel (IQR - 3.1 to - 10.1). MD was strongly correlated with clinical severity (r = - 0.94, P < 0.0001), and were used for severity of defects cut-off values: (1) normal > - 2 dB, (2) mild - 2 dB to - 4 dB, (3) moderate - 4 to - 8 dB, (4) severe - 8 to - 17 dB, (5) very severe < - 17 dB.
CONCLUSION
Surgical decompression is highly effective in improving visual function. Uniform, quantitative grading of visual dysfunction was lacking. MD is a promising quantitative outcome measure. We provide recommendations for the evaluation of timing of surgery, considering severity of visual impairment, which will need further validation based on expert clinical practice.
Topics: Adenoma; Cohort Studies; Decompression, Surgical; Female; Hemianopsia; Humans; Male; Middle Aged; Optic Chiasm; Pituitary Neoplasms; Quality of Health Care; Recovery of Function; Severity of Illness Index; Time Factors; Treatment Outcome; Tumor Burden; Vision Disorders; Visual Acuity; Visual Field Tests
PubMed: 32419072
DOI: 10.1007/s11102-020-01044-0 -
Acta Neurochirurgica Jun 2020Pituitary adenomas (PA) are common intracranial tumors. In the context of the aging of the population, the question is whether postsurgical outcomes are comparable to... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Pituitary adenomas (PA) are common intracranial tumors. In the context of the aging of the population, the question is whether postsurgical outcomes are comparable to the younger ones. The primary objective of the present study was to review published resection and recurrence rates after transsphenoidal resection. The secondary aim was to evaluate visual improvement and complication rates.
METHODS
The authors searched PubMed and Medline databases, of published English series, with no time frame limit, evaluating outcomes of transsphenoidal resection in populations aged more or less than 65, 70, and 80 years. We performed a systematic review and meta-analysis.
RESULTS
Median overall resection rates for younger population was 70.7% (range 54-76.8) and for elderly one was 65.7% (range 16.6-78.2) (two-sample t test, p = 0.35). The only statistically significant difference for gross total resection rates (GTR) favored patients aged less than 80 (p = 0.01). There was no statistically significant difference among recurrence rates. There was a statistically significant difference for visual improvement favoring patients aged more than 80 (p = 0.03). For the age groups of less versus more than 70, there was a statistically significant difference for overall complication rate favoring younger groups (p < 0.05).
CONCLUSION
Present data shows GTR rates favoring younger patients. Recurrence rates remain similar over the mean follow-up period. Moreover, visual improvement favors patients aged more than 80. Overall complication rates favor patients younger than 70, which might be also related to additional comorbidities, frequently present in seniors. Transsphenoidal surgery is safe and effective even for older patients.
Topics: Adenoma; Adult; Age Factors; Aged; Aged, 80 and over; Female; Humans; Male; Middle Aged; Neurosurgical Procedures; Pituitary Neoplasms; Postoperative Complications
PubMed: 32221730
DOI: 10.1007/s00701-020-04300-1 -
BMC Cancer Dec 2019Cranial radiotherapy (cRT) can induce hormonal deficiencies as a consequence of significant doses to the hypothalamic-pituitary (HP) axis. In contrast to profound...
BACKGROUND
Cranial radiotherapy (cRT) can induce hormonal deficiencies as a consequence of significant doses to the hypothalamic-pituitary (HP) axis. In contrast to profound endocrinological follow-up data from survivors of childhood cancer treated with cRT, little knowledge exists for adult cancer patients.
METHODS
A systematic search of the literature was conducted using the PubMed database and the Cochrane library offering the basis for our debate of the relevance of HP axis impairment after cRT in adult cancer patients. Against the background of potential relevance for patients receiving whole brain radiotherapy (WBRT), a particular focus was set on the temporal onset of hypopituitarism and the radiation dose to the HP axis.
RESULTS
Twenty-eight original papers with a total of 1728 patients met the inclusion criteria. Radiation doses to the HP area ranged from 4 to 97 Gray (Gy). Hypopituitarism incidences ranged from 20 to 93% for adult patients with nasopharyngeal cancer or non-pituitary brain tumors. No study focused particularly on hypopituitarism after WBRT. The onset of hypopituitarism occurred as early as within the first year following cRT (range: 3 months to 25.6 years). However, since most studies started follow-up evaluation only several years after cRT, early onset of hypopituitarism might have gone unnoticed.
CONCLUSION
Hypopituitarism occurs frequently after cRT in adult cancer patients. Despite the general conception that it develops only after several years, onset of endocrine sequelae can occur within the first year after cRT without a clear threshold. This finding is worth debating particularly in respect of treatment options for patients with brain metastases and favorable survival prognoses.
Topics: Brain Neoplasms; Cranial Irradiation; Humans; Hypopituitarism; Hypothalamus; Pituitary Gland; Radiation Injuries; Randomized Controlled Trials as Topic
PubMed: 31830931
DOI: 10.1186/s12885-019-6431-5 -
Neuro-oncology Mar 2020This systematic review reports on outcomes and toxicities following stereotactic radiosurgery (SRS) for non-functioning pituitary adenomas (NFAs) and presents consensus... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This systematic review reports on outcomes and toxicities following stereotactic radiosurgery (SRS) for non-functioning pituitary adenomas (NFAs) and presents consensus opinions regarding appropriate patient management.
METHODS
Using the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, a systematic review was performed from articles of ≥10 patients with NFAs published prior to May 2018 from the Medline database using the key words "radiosurgery" and "pituitary" and/or "adenoma." Weighted random effects models were used to calculate pooled outcome estimates.
RESULTS
Of the 678 abstracts reviewed, 35 full-text articles were included describing the outcomes of 2671 patients treated between 1971 and 2017 with either single fraction SRS or hypofractionated stereotactic radiotherapy (HSRT). All studies were retrospective (level IV evidence). SRS was used in 27 studies (median dose: 15 Gy, range: 5-35 Gy) and HSRT in 8 studies (median total dose: 21 Gy, range: 12-25 Gy, delivered in 3-5 fractions). The 5-year random effects local control estimate after SRS was 94% (95% CI: 93.0-96.0%) and 97.0% (95% CI: 93.0-98.0%) after HSRT. The 10-year local control random effects estimate after SRS was 83.0% (95% CI: 77.0-88.0%). Post-SRS hypopituitarism was the most common treatment-related toxicity observed, with a random effects estimate of 21.0% (95% CI: 15.0-27.0%), whereas visual dysfunction or other cranial nerve injuries were uncommon (range: 0-7%).
CONCLUSIONS
SRS is an effective and safe treatment for patients with NFAs. Encouraging short-term data support HSRT for select patients, and mature outcomes are needed before definitive recommendations can be made. Clinical practice opinions were developed on behalf of the International Stereotactic Radiosurgery Society (ISRS).
Topics: Adenoma; Disease Management; Humans; Pituitary Neoplasms; Radiation Dose Hypofractionation; Radiosurgery; Societies, Medical; Treatment Outcome
PubMed: 31790121
DOI: 10.1093/neuonc/noz225 -
BMC Cancer Nov 2019Intracranial metastasis of Gastrointestinal Stromal Tumors (GISTs) is rare but presents unique treatment challenges. We present a case of intracranial metastasis of GIST...
BACKGROUND
Intracranial metastasis of Gastrointestinal Stromal Tumors (GISTs) is rare but presents unique treatment challenges. We present a case of intracranial metastasis of GIST with a systematic review of the literature. A literature search using key terms "'gastrointestinal stromal tumor' AND brain AND metastasis"" was conducted through May 2019 via Embase and Pubmed according to PRISMA guidelines. Only cases describing intradural metastases rather than calvarial or intraorbital metastases were included.
CASE PRESENTATION
A 57-year-old woman with history of GIST metastatic to the liver presented with a six-week history of left facial weakness, left hearing loss, and left facial numbness, and a one-week history of headaches, gait disturbance, and dizziness. MRI revealed a contrast-enhancing dural-based left middle cranial fossa mass measuring 2.9 cm × 3.1 cm × 3.4 cm with extension into the internal auditory canal and cerebral edema. A left temporal craniotomy was performed to excise the lesion, and the patient was discharged to a rehabilitation facility at her preoperative baseline. Intraoperative pathology revealed a spindle cell neoplasm, postoperative MRI demonstrated gross total resection of the lesion, and microscopic analysis demonstrated sheets of spindled tumor cells with short ovoid, irregular, hyperchromatic nuclei and scattered large atypical nuclei without extensive necrosis. Immunohistochemical staining was positive for KIT proto-oncogene (CD117, c-KIT), and the patient was put on imatinib (400 mg/day).
CONCLUSIONS
Of the 18 cases analyzed and our present case, metastasis typically involved the cerebrum with only one in infratentorial elements. The tumors in seven of the cases involved the dura, and one case metastasized to the pituitary. Eight patients died following treatment. Surgery remains the mainstay of intracranial metastatic GIST, however there are many reports of good responses to radiation or chemotherapy alone. More investigation is required to determine the best treatment course for these patients.
Topics: Brain Neoplasms; Female; Gastrointestinal Neoplasms; Gastrointestinal Stromal Tumors; Humans; Middle Aged; Prognosis; Proto-Oncogene Mas
PubMed: 31730471
DOI: 10.1186/s12885-019-6316-7 -
Cancer Medicine Dec 2019With the growing use of immune checkpoint inhibitors (ICIs), case reports of rare yet life-threatening pituitary-adrenal dysfunctions, particularly for hypopituitarism,... (Meta-Analysis)
Meta-Analysis
With the growing use of immune checkpoint inhibitors (ICIs), case reports of rare yet life-threatening pituitary-adrenal dysfunctions, particularly for hypopituitarism, are increasingly being published. In this analysis, we focus on these events by including the most recent publications and reports from early phase I/II and phase III clinical trials and comparing the incidence and risks across different ICI regimens. PubMed, Embase, and the Cochrane Library were systematically searched from inception to April 2019 for clinical trials that reported on pituitary-adrenal dysfunction. The rates of events, odds ratios (ORs), and 95% confidence intervals (CIs) were obtained using random effects meta-analysis. The analyses included data from 160 trials involving 40 432 participants. The rate was 2.43% (95% CI, 1.73%-3.22%) for all-grade adrenal insufficiency and 3.25% (95% CI, 2.15%-4.51%) for hypophysitis. Compared with the placebo or other therapeutic regimens, ICI agents were associated with a higher incidence of serious-grade adrenal insufficiency (OR 3.19, 95% CI, 1.84 to 5.54) and hypophysitis (OR 4.77, 95% CI, 2.60 to 8.78). Among 71 serious-grade hypopituitarism instances in 12 336 patients, there was a significant association between ICIs and hypopituitarism (OR 3.62, 95% CI, 1.86 to 7.03). Substantial heterogeneity was noted across the studies for the rates of these events, which in part was attributable to the different types of ICIs and varied phases of the clinical trials. Although the rates of these events were low, the risk was increased following ICI-based treatment, particularly for CTLA-4 inhibitors, which were associated with a higher incidence of pituitary-adrenal dysfunction than PD-1/PD-L1 inhibitors.
Topics: Adrenal Insufficiency; Antineoplastic Agents, Immunological; Biomarkers, Tumor; CTLA-4 Antigen; Clinical Trials as Topic; Humans; Hypopituitarism; Neoplasms; Odds Ratio; Pituitary-Adrenal Function Tests; Pituitary-Adrenal System; Programmed Cell Death 1 Receptor; Severity of Illness Index
PubMed: 31679184
DOI: 10.1002/cam4.2661