Ki-67/MIB-1 and Recurrence in Pituitary Adenoma

2021 ◽  
Author(s):  
Kent Tadokoro ◽  
Colten Wolf ◽  
Joseph Toth ◽  
Cara Joyce ◽  
Meharvan Singh ◽  
...  
Keyword(s):  
Systematic Review ◽  
Pituitary Adenoma ◽  
Recurrence Rate ◽  
Pituitary Adenomas ◽  
Cellular Proliferation ◽  
Published Data ◽  
Ki 67 ◽  
Institutional Data ◽  
Mib 1

Abstract Objectives Ki-67/MIB-1 is a marker of cellular proliferation used as a pathological parameter in the clinical assessment of pituitary adenomas, where its expression has shown utility in predicting the invasiveness of these tumors. However, studies have shown variable results when using Ki-67/MIB-1 association with recurrence. The purpose of this study is to determine if a high Ki-67/MIB-1 labeling index (LI) is predictive of recurrence in pituitary adenomas. Methods A retrospective chart review was performed for patients undergoing pituitary adenoma resection with at least 1 year of follow-up. Additionally, systematic data searches were performed and included studies that correlated recurrence rate to Ki-67/MIB-1 LI. Our institutional data were included in a synthesis with previously published data. Results Our institutional review included 79 patients with a recurrence rate of 26.6%. We found that 8.8% of our patients had a high Ki-67/MIB-1 LI (>3%); however, high Ki-67/MIB-1 was not associated with recurrence. The systematic review identified 244 articles and 49 full-text articles that were assessed for eligibility. Quantitative analysis was performed on 30 articles including our institutional data and 18 studies reported recurrence by level of Ki-67/MIB-1 LI. Among studies that compared Ki-67/MIB-1 ≥3 vs. <3%, 10 studies reported odds ratios (OR) greater than 1 of which 6 were statistically significant. A high Ki-67/MIB-1 had higher odds of recurrence via the pooled odds ratio (OR = 4.15, 95% confidence interval [CI]: 2.31–7.42). Conclusion This systematic review suggests that a high Ki-67/MIB-1 should prompt an increased duration of follow-up due to the higher odds of recurrence of pituitary adenoma.

scholarly journals Pediatric Pituitary Adenoma: Case Series, Review of the Literature, and a Skull Base Treatment Paradigm

2018 ◽  
Vol 79 (01) ◽  
pp. 091-114 ◽  
Author(s):  
Avital Perry ◽  
Christopher Graffeo ◽  
Christopher Marcellino ◽  
Bruce Pollock ◽  
Nicholas Wetjen ◽  
...  
Keyword(s):  
Systematic Review ◽  
Pituitary Adenoma ◽  
Skull Base ◽  
Pituitary Adenomas ◽  
Pediatric Population ◽  
Csf Leak ◽  
Persistent Disease ◽  
Treatment Paradigm ◽  
Surgical Cure

Background Pediatric pituitary adenoma is a rare skull base neoplasm, accounting for 3% of all intracranial neoplasms in children and 5% of pituitary adenomas. Compared with pituitary tumors in adults, secreting tumors predominate and longer disease trajectories are expected due to the patient age resulting in a natural history and treatment paradigm that is complex and controversial. Objectives The aims of this study were to describe a large, single-institution series of pediatric pituitary adenomas with extensive long-term follow-up and to conduct a systematic review examining outcomes after pituitary adenoma surgery in the pediatric population. Methods The study cohort was compiled by searching institutional pathology and operative reports using diagnosis and site codes for pituitary and sellar pathology, from 1956 to 2016. Systematic review of the English language literature since 1970 was conducted using PubMed, MEDLINE, Embase, and Google Scholar. Results Thirty-nine surgically managed pediatric pituitary adenomas were identified, including 15 prolactinomas, 14 corticotrophs, 7 somatotrophs, and 4 non-secreting adenomas. All patients underwent transsphenoidal resection (TSR) as the initial surgical treatment. Surgical cure was achieved in 18 (46%); 21 experienced recurrent/persistent disease, with secondary treatments including repeat surgery in 10, radiation in 14, adjuvant pharmacotherapy in 11, and bilateral adrenalectomy in 3. At the last follow-up (median 87 months, range 3–581), nine remained with recurrent/persistent disease (23%).Thirty-seven publications reporting surgical series of pediatric pituitary adenomas were included, containing 1,284 patients. Adrenocorticotropic hormone (ACTH)-secreting tumors were most prevalent (43%), followed by prolactin (PRL)-secreting (37%), growth hormone (GH)-secreting (12%), and nonsecreting (7%). Surgical cure was reported in 65%. Complications included pituitary insufficiency (23%), permanent visual dysfunction (6%), chronic diabetes insipidus (DI) (3%), and postoperative cerebrospinal fluid (CSF) leak (4%). Mean follow-up was 63 months (range 0–240), with recurrent/persistent disease reported in 18% at the time of last follow-up. Conclusion Pediatric pituitary adenomas are diverse and challenging tumors with complexities far beyond those encountered in the management of routine adult pituitary disease, including nuanced decision-making, a technically demanding operative environment, high propensity for recurrence, and the potentially serious consequences of hypopituitarism with respect to fertility and growth potential in a pediatric population. Optimal treatment requires a high degree of individualization, and patients are most likely to benefit from consolidated, multidisciplinary care in highly experienced centers.

Aggressive Cushing disease five years after the treatment of a nonfunctional pituitary adenoma

2016 ◽  
Vol 62 (5) ◽  
pp. 77-78
Author(s):  
Minodora Betivoiu ◽  
Sorina Martin ◽  
Iulia Soare ◽  
Alexandra Nila ◽  
Simona Fica
Keyword(s):  
Pituitary Adenoma ◽  
Gamma Knife ◽  
Pituitary Adenomas ◽  
Histopathological Examination ◽  
Case Reports ◽  
Dependent Diabetes Mellitus ◽  
Ki 67 ◽  
The Right ◽  
Gamma Knife Therapy

Introduction. Cushing's disease (CD) represents 10%–12% of all pituitary adenomas and is seen predominantly in women, with a female-to-male ratio of 8:1. Although most patients with ACTH-secreting adenomas present with benign, small tumors, some have invasive macroadenomas. Rarely, nonfunctional pituitary adenomas (NFPAs) may gain secretory function, but there have been a few case reports of metamorphosis to CD.Case report. We report the case of a 59-year-old female diagnosed in 2007 with a NFPA and panhypopituitarism. She had two transsphenoidal surgeries and Gamma Knife therapy and started replacement treatment with levothyroxine 75mcg/day and prednisone 5mg/day. The postoperative course was favorable and imagistic follow-up between 2007-2014 showed progressive reduction of the residual tumor and empty sella. From personal history we note noninsulin-dependent diabetes mellitus, postmenopausal osteoporosis treated with bisphosphonates. In January 2015 she suffered visual loss on the right eye. Pituitary MRI showed supra and parasellar tumor recurrence of 27/24/17mm, infiltrating the right side of the cavernous sinus, extending around the right internal carotid artery and optic nerve, compressing the optic chiasm. In March 2015 a third transsphenoidal partial excision of the tumor was performed and in August Gamma Knife therapy was repeated. The histopathological examination was consistent with a pituitary adenoma but immunohistochemical staining for ACTH was positive, with Ki-67=25%. She had no non-specific cushingoid features. Laboratory test: glucose=116mg/dl, HbA1c=7.5%, FSH=3.34mIU/ml, LH=0.585mIU/ml TSH=0.044mcIU/ml, FT4=1.13ng/dl. Prednisone replacement therapy was stopped and CD was confirmed: 8AMcortisol=13.3mcg/dl, 23PMcortisol=11.3mcg/dl, ACTH=70.2pg/ml, 8AMcortisol after 1mg dexamethasone overnight=13.8mcg/dl. Ophthalmic exam: blindness in the right eye, slightly decreased visual field in the left eye. Pituitary MRI 8-month postsurgery revealed a 28/31/28mm invasive tumor. We started treatment with Cabergoline 3mg/week and recommended closely biological and imagistic follow-up, hoping for a good response to radiotherapy.Conclusions: Our case stresses the importance of regular, lifelong follow-up of patients with NFPAs. Chiloiro et al have reported that pituitary adenomas with Ki-67≥1.5% have a higher risk of recurrence. Although the characteristics of patients with CD have been well known for decades, the diagnosis and management of this disease are often challenging.

Recurrence Rate of Sporadic Pheochromocytomas After Curative Adrenalectomy: A Systematic Review and Meta-analysis

2020 ◽  
Author(s):  
Isabelle Holscher ◽  
Tijs J van den Berg ◽  
Koen M A Dreijerink ◽  
Anton F Engelsman ◽  
Els J M Nieveen van Dijkum
Keyword(s):  
Systematic Review ◽  
Recurrence Rate ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Weighted Mean ◽  
Curative Surgery ◽  
Endocrine Society ◽  
Time To Recurrence ◽  
The Cochrane Library

Abstract Background Evidence on follow-up duration for patients with sporadic pheochromocytomas is absent, and current guidelines of the European Society of Endocrinology, American Association of Clinical Endocrinologists and Endocrine Surgeons, and the Endocrine Society are ambiguous about the appropriate duration of follow-up. The aim of this systematic review and meta-analysis is to evaluate the recurrence rate of sporadic pheochromocytomas after curative adrenalectomy. Materials and Methods A literature search in PubMed, Embase, and the Cochrane Library was performed. A study was eligible if it included a clear report on the number of sporadic patients, recurrence rate, and follow-up duration. Studies with an inclusion period before 1990, &lt;2 years of follow-up, &lt;10 patients, and unclear data on the sporadic nature of pheochromocytomas were excluded. A meta-analysis on recurrence was performed provided that the heterogeneity was low (I2 &lt; 25%) or intermediate (I2 26–75%). Hozo’s method was used to calculate weighted mean follow-up duration and weighted time to recurrence with combined standard deviations (SDs). Results A total of 13 studies, including 430 patients, were included in the synthesis. The meta-analysis results describe a pooled recurrence rate after curative surgery of 3% (95% confidence interval: 2–6%, I2 = 0%), with a weighted mean time to recurrence of 49.4 months (SD = 30.7) and a weighted mean follow-up period of 77.3 months (SD = 32.2). Conclusions This meta-analysis shows a very low recurrence rate of 3%. Prospective studies, including economical and health effects of limited follow-up strategies for patients with truly sporadic pheochromocytomas should be considered.

scholarly journals Oral Fluoroquinolone or Trimethoprim-Sulfamethoxazole vs ß-Lactams as Step-Down Therapy for Enterobacteriaceae Bacteremia: Systematic Review and Meta-analysis

2019 ◽  
Vol 6 (10) ◽  
Author(s):  
Chitra Punjabi ◽  
Vivian Tien ◽  
Lina Meng ◽  
Stan Deresinski ◽  
Marisa Holubar
Keyword(s):  
Systematic Review ◽  
Oral Treatment ◽  
Meta Analysis ◽  
Published Data ◽  
All Cause Mortality ◽  
Dosing Regimens ◽  
Step Down ◽  
Selection Of ◽  
Infection Recurrence

Abstract Background Using published data, we sought to compare outcomes in patients transitioned to either oral fluoroquinolones (FQs) or trimethoprim-sulfamethoxazole (TMP-SMX) vs ß-lactams (BLs) after an initial intravenous (IV) course for gram-negative rod (GNR) bacteremia. Methods We conducted a systematic review of PubMed and EMBASE and published IDWeek abstracts. We included studies that reported all-cause mortality and/or infection recurrence in patients transitioned to oral FQ/TMP-SMX and BLs. Results Eight retrospective studies met inclusion criteria with data for 2289 patients, of whom 65% were transitioned to oral FQs, 7.7% to TMP-SMX, and 27.2% to BLs. Follow-up periods ranged from 21 to 90 days. All-cause mortality was not significantly different between patients transitioned to either FQ/TMP-SMX or BLs (odds ratio [OR], 1.13; 95% confidence interval [CI], 0.69–1.87). Overall recurrence of infection, either bacteremia or the primary site, occurred more frequently in patients transitioned to oral BLs vs FQs (OR, 2.05; 95% CI, 1.17–3.61). Analysis limited to recurrent bacteremia was similarly suggestive, although limited by small numbers (OR, 2.15; 95% CI, 0.93–4.99). However, based on known pharmacokinetics/pharmacodynamics, prescribed ß-lactam dosing regimens were frequently suboptimal. Conclusions In the step-down IV to oral treatment of GNR bacteremia, we found insufficient data regarding outcomes after oral TMP-SMX; however, selection of an FQ over commonly utilized ß-lactam regimens may reduce chances of infection recurrence. Although this may be a class effect, it may simply be the result of inadequate dosing of ß-lactams. Additional investigations are warranted to determine outcomes with TMP-SMX and optimized oral ß-lactam dosing regimens.

Residual nonfunctioning pituitary adenomas: prognostic value of MIB-1 labeling index for tumor progression

2009 ◽  
Vol 111 (3) ◽  
pp. 563-571 ◽  
Author(s):  
Georg Widhalm ◽  
Stefan Wolfsberger ◽  
Matthias Preusser ◽  
Ingeborg Fischer ◽  
Adelheid Woehrer ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Pituitary Adenomas ◽  
Residual Tumor ◽  
Labeling Index ◽  
Ki 67 ◽  
Nonfunctioning Pituitary Adenomas ◽  
Time Period ◽  
Tumor Group ◽  
Significant Difference ◽  
Mib 1

Object In residual nonfunctioning pituitary adenomas, reliable prognostic parameters indicating probability of tumor progression are needed. The Ki 67 expression/MIB-1 labeling index (LI) is considered to be a promising candidate factor. The aim in the present study was to analyze the clinical usefulness of MIB-1 LI for prognosis of tumor progression. Methods The authors studied a cohort of 92 patients with nonfunctioning pituitary adenomas. Based on sequential postoperative MR images, patients were classified as tumor free (51 patients) or as harboring residual tumor (41 individuals). The residual tumor group was further subdivided in groups with stable residual tumors (14 patients) or progressive residual tumors (27 patients). The MIB-1 LI was assessed in tumor specimens obtained in all patients, and statistical comparisons of MIB-1 LI of the various subgroups were performed. Results . The authors found no significant difference of MIB-1 LI in the residual tumor group compared with the tumor-free group. However, MIB-1 LI was significantly higher in the progressive residual tumor group, compared with the stable residual tumor group. Additionally, the time period to second surgery was significantly shorter in residual adenomas showing an MIB-1 LI > 3%. Conclusions The data indicate that MIB-1 LI in nonfunctioning pituitary adenomas is a clinically useful prognostic parameter indicating probability of progression of postoperative tumor remnants. The MIB-1 LI may be helpful in decisions of postoperative disease management (for example, frequency of radiographic intervals, planning for reoperation, radiotherapy, and/or radiosurgery).

Clinical significance of proliferative activity evaluated by MIB-1 in the treatment and postoperative follow-up of early breast cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21054-21054
Author(s):  
R. Nishimura ◽  
N. Arima
Keyword(s):  
Breast Cancer ◽  
Adjuvant Therapy ◽  
Recurrence Rate ◽  
Clinical Significance ◽  
Proliferative Activity ◽  
Disease Free Survival ◽  
Her2 Status ◽  
City Hospital ◽  
Mib 1

21054 Background: To evaluate a clinical significance of proliferative activity in breast cancer, we studied relationships between proliferative activity and recurrence rate, the time of recurrence or adjuvant therapy. Methods: We analyzed 2448 patients with primary breast cancer between 1987 and 2004 in the Kumamoto City Hospital, and 437 cases out of the patients developed recurrence. Furthermore, the rate of recurrence before and after 1999 when postoperative adjuvant therapy (such as CEF or Taxanes) was started as standard treatment was investigated. Proliferative activity was judged by immunostaining for MIB-1. The fraction of proliferating cells was classified into 3 degrees (=19%, 20–49%, 50%=). Median observation period was 70 months. Results: 1) Distribution of patients by proliferation was as follows; =19%:1215 cases(50%), 20–49%: 870 cases(35%), or 50%=: 363 cases(15%). There was a significant relationship between proliferative activity and tumor size, nodal status, ER, PgR, p53 or HER2 status. 2) Multivariate analysis for disease-free survival revealed that a proliferative activity was one of significant factors in node-negative and positive cases. Recurrence rate was 11.6% in cases with low proliferation and 31.0% in high proliferation. The mean period from operation to recurrence in cases with low proliferation was 50.2 months, whereas 19.9 months in high proliferation (p<0.0001). Moreover, 74% of recurrent cases with high proliferation recurred within 2 years after operation, and there were few recurrences from the fifth year. 3) Patients with low proliferation frequently developed bone metastasis. In local recurrence, diffuse skin recurrence was often seen in cases with high proliferation. 4) The prognosis of patients in the later period (standard therapy group) was significantly better than that of patients in the earlier period, especially in high proliferation group. Conclusions: Proliferative activity might reflect aggressive behavior of breast cancer and predict the time of recurrence. The standard adjuvant therapy was effective in inhibiting early recurrence with high proliferation. It is important to take proliferative activity into consideration in the treatment and follow-up of breast cancer. No significant financial relationships to disclose.

scholarly journals Evaluation of prognostic utility of MIB-1 and p53 expression in pituitary adenomas: correlations with clinical behaviour and follow-up results

2014 ◽  
Vol 28 (3) ◽  
pp. 502-507 ◽  
Author(s):  
Asen Hadzhiyanev ◽  
Radina Ivanova ◽  
Emil Nachev ◽  
Atanaska Elenkova ◽  
Maria Yaneva ◽  
...  
Keyword(s):  
Pituitary Adenomas ◽  
P53 Expression ◽  
Clinical Behaviour ◽  
Prognostic Utility ◽  
Mib 1

Atypical pituitary adenomas: incidence, clinical characteristics, and implications

2011 ◽  
Vol 114 (2) ◽  
pp. 336-344 ◽  
Author(s):  
Gabriel Zada ◽  
Whitney W. Woodmansee ◽  
Shakti Ramkissoon ◽  
Jordan Amadio ◽  
Vania Nose ◽  
...  
Keyword(s):  
Pituitary Adenomas ◽  
Immunohistochemical Analysis ◽  
Null Cell ◽  
Cell Adenoma ◽  
Null Cell Adenoma ◽  
Tumor Subtypes ◽  
P53 Immunoreactivity ◽  
Mib 1

Object The 2004 WHO classification of pituitary adenomas now includes an “atypical” variant, defined as follows: MIB-1 proliferative index greater than 3%, excessive p53 immunoreactivity, and increased mitotic activity. The authors review the incidence of this atypical histopathological subtype and its correlation with tumor subtype, invasion, and surgical features. Methods The records of 121 consecutive patients who underwent transsphenoidal surgery for pituitary adenomas during an 18-month period were retrospectively reviewed for evidence of atypical adenomas. Results Eighteen adenomas (15%) met the criteria for atypical lesions; 17 (94%) of the 18 were macroadenomas. On imaging, 15 (83%) demonstrated imaging evidence of surrounding invasion, compared with 45% of typical adenomas (p = 0.004). Atypical tumors occurred in 12 female (67%) and 6 male (33%) patients. Patient age ranged from 16 to 70 years (mean 48 years). Nine patients (50%) had hormonally active tumors, and 9 had nonfunctional lesions. Four (22%) of the 18 patients presented to us with recurrent tumors. Immunohistochemical analysis demonstrated the following tumor subtypes: GH-secreting adenoma with plurihormonal staining (5 patients [28%]); null-cell adenoma (5 patients [28%]); silent ACTH tumor (3 patients [17%]), ACTH-staining tumor with Cushing's disease (2 patients [11%]), prolactinoma (2 patients [11%]), and silent FSH-staining tumor (1 patient [6%]). The MIB-1 labeling index ranged from 3% to 20% (mean 7%). Conclusions Atypical tumors were identified in 15% of resected pituitary adenomas, and they tended to be aggressive, invasive macroadenomas. More longitudinal follow-up is required to determine whether surgical outcomes, potential for recurrence, or metastasis of atypical adenomas vary significantly from their typical counterparts.

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