scholarly journals Factors That Predict the Growth of Residual Nonfunctional Pituitary Adenomas: Correlations between Relapse and Cell Cycle Markers

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Petr Matoušek ◽  
Petr Buzrla ◽  
Štefan Reguli ◽  
Jan Krajča ◽  
Jana Dvořáčková ◽  
...  

Introduction. Nonfunctional pituitary adenomas are treated surgically, and even partial resection can improve or eliminate clinical symptoms. Notably, progression requires further intervention, which presents an increased risk, especially in older patients. This study investigated whether the histopathological characteristics of nonfunctional adenomas could predict recurrence. Materials and Methods. Data were obtained retrospectively from 30 patients who underwent surgery for the partial resection of pituitary adenomas. Remnant tumor growth was observed in 17 patients, while the residual tumor was unchanged more than 7 years after surgery in 13 patients. Statistical analysis was performed to investigate correlations between remnant tumor progression and tumor histopathological findings, including protein expression of p21, p27, p53, and Ki-67. Results and Discussion. Remnant tumors that demonstrated regrowth showed significantly higher protein expression of p21 and Ki-67. Expression of the p53 tumor suppressor was also higher in this group, but the difference was at the limit of statistical significance. Conclusion. Tumors with high expression of p21 and p53 and with a high Ki-67 index were more likely to show residual pituitary adenoma progression. Such cases should undergo frequent radiological examination and timely reoperation, and radiosurgery should be considered.

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Hugo Valente do Couto ◽  
Bruna Peres ◽  
Klevia Sampaio ◽  
Nina de Castro Musolino ◽  
Valter Cescato ◽  
...  

Abstract Introduction: Typical ACTH-producing pituitary adenomas are benign tumors, microadenomas, successfully treated by neurosurgery. However, 10-20% of Cushing’s disease (CD) patients have macroadenomas, sometimes invasive and aggressive cases with poorer surgical prognosis needing additional approaches. Temozolomide (TMZ), second generation alkylating agent, has been used alone or in combination to other medications/radiotherapy (RTX) for tumor control of aggressive pituitary adenomas and carcinomas. We report one patient with giant aggressive corticotropinoma that presented control tumor with RTX and TMZ after four pituitary surgeries unable to uncontroll tumor growth. Clinical Case: A 18-year-old female patient presented with weight gain, red moon face, supraclavicular fullness, dorsal hump, large purple striae, acanthosis nigricans, secondary amenorrhea, frontotemporal headache, visual impairment and right palpebral ptosis. Hormonal analysis confirmed ACTH-dependent Cushing's syndrome. Pituitary MRI showed the presence of a large selar and suprasellar expansive lesion of 5.2X5.1X4.0 cm with displacement of third ventricle, hypothalamus and lateral ventricles. The patient was submitted to the first neurosurgery (transsphenoidal route) with partial resection. Pathological analyses confirmed pituitary adenoma positive for ACTH, Ki-67 8%, negative p53 and 7 mitoses/10 field of great increase. Subsequent surgery was done by craniotomy with partial resection. Cabergoline 2 mg/week was started but the tumor keeps growing with worsening of visual complaints and increase of cortisol levels. At admission in our center, we planned new surgeries do remove the maximal tumor possible (debulking) and subsequent RTX and TMZ. She was submitted to third surgery by transsphenoidal route and the last surgical procedure by craniotomy. MRI pre-RTX done three months after the 4th surgery showed remnant tumor of 3.5X3.0X3.0 cm. Fractioned stereotaxic radiotherapy was done with linear accelerator in a total of 54 Gy divided in 30 sessions. TMZ was initiated in a dose of 150 m2/day, cycles of five days/month, using for 14 months. Pituitary MRI 3, 6 and 10 months after TMZ showed a small reduction of tumor with increase of intratumor cystic areas. Conclusion: The combined use of TMZ and radiotherapy is an important approach for the treatment of rapidly growing, aggressive pituitary ACTH-secreting tumors resistant to conventional treatment.


2009 ◽  
Vol 111 (3) ◽  
pp. 563-571 ◽  
Author(s):  
Georg Widhalm ◽  
Stefan Wolfsberger ◽  
Matthias Preusser ◽  
Ingeborg Fischer ◽  
Adelheid Woehrer ◽  
...  

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).


2021 ◽  
Vol 57 (1) ◽  
pp. 20
Author(s):  
Puguh Setyo Nugroho ◽  
Muhtarum Yusuf ◽  
Titiek Ahadiyah Hidayati

Several studies showed that the index of nasopharyngeal carcinoma (NPC) cell growth could be used to assess the carcinogenesis interaction factor, development and prognosis of NPC. Cell proliferation index could always be assessed with Ki-67 protein expression test. This research was conducted to study the correlation between cell proliferation index with cervical lymphoid node status in NPC in clinical manifestation to asses the progressivity and prognosis on NPC patients. This study used cross sectional design. Biopsy tissue specimen were acquired from 35 NPC patients clinically divided into four criteria of cervical lymphoid node status (N0, N1, N2 and N3). Expression of Ki-67 protein was acquired by immunohistochemistry test using monoclonal rabbit antibody anti-human Ki-67 clone 901-325-091911 (Biocare Medical, LCC. 4040 Pike Line, CA 94520 USA). The measurement of Ki-67 protein was conducted by pathology consultant. Spearman statistic test was performed to asses the correlation between Ki-67 protein expression and cervical lymphoid node status. The statistical significance was defined as p<0.05. Positive expression of Ki-67 protein was found in 33 patients; 4 patients with N0 (11.43%), 5 patients with N1 (14.29%), 9 patients with N2 (25.71%), and 15 patients with N3. Negative expression of Ki-67 protein was found in 2 patients with N0 (5.71%). The Spearman test resulted at p=0.0001 with correlation coefficient of 0.758. The correlation between Ki-67 protein expression with cervical lymphoid node resulted in a significant correlation (p<0.05). In conclusion, cell proliferation index has correlation with cervical lymphoid node status in NPC patients.


2021 ◽  
Vol 12 ◽  
Author(s):  
Yike Chen ◽  
Feng Cai ◽  
Jing Cao ◽  
Feng Gao ◽  
Yao Lv ◽  
...  

BackgroundPituitary adenoma (PA) is a benign neuroendocrine tumor caused by adenohypophysial cells, and accounts for 10%-20% of all primary intracranial tumors. The surgical outcomes and prognosis of giant pituitary adenomas measuring ≥3 cm in diameter differ significantly due to the influence of multiple factors such as tumor morphology, invasion site, pathological characteristics and so on. The aim of this study was to explore the risk factors related to the recurrence or progression of giant and large PAs after transnasal sphenoidal surgery, and develop a predictive model for tumor prognosis.MethodsThe clinical and follow-up data of 172 patients with large or giant PA who underwent sphenoidal surgery at the Second Affiliated Hospital of Zhejiang University School of Medicine from January 2011 to December 2017 were retrospectively analyzed. The basic clinical information (age, gender, past medical history etc.), imaging features (tumor size, invasion characteristics, extent of resection etc.), and histopathological characteristics (pathological results, Ki-67, P53 etc.) were retrieved. SPSS 21.0 software was used for statistical analysis, and the R software was used to establish the predictive nomogram.ResultsSeventy out of the 172 examined cases (40.7%) had tumor recurrence or progression. The overall progress free survival (PFS) rates of the patients at 1, 3 and 5 years after surgery were 90.70%, 79.65% and 59.30% respectively. Log-rank test indicated that BMI (P &lt; 0.001), Knosp classification (P &lt; 0.001), extent of resection (P &lt; 0.001), Ki-67 (P &lt; 0.001), sphenoidal sinus invasion (P = 0.001), Hardy classification (P = 0.003) and smoking history (P = 0.018) were significantly associated with post-surgery recurrence or progression. Cox regression analysis further indicated that smoking history, BMI ≥25 kg/m2, Knosp classification grade 4, partial resection and ≥3% Ki-67 positive rate were independent risk factors of tumor recurrence or progression (P &lt; 0.05). In addition, the nomogram and ROC curve based on the above results indicated significant clinical value.ConclusionThe postoperative recurrence or progression of large and giant PAs is related to multiple factors and a prognostic nomogram based on BMI (≥25 kg/m2), Knosp classification (grade 4), extent of resection (partial resection) and Ki-67 (≥3%) can predict the recurrence or progression of large and giant PAs after transnasal sphenoidal surgery.


2019 ◽  
Vol 3 (10) ◽  
pp. 1931-1941
Author(s):  
Jelena Maletkovic ◽  
Asmaa Dabbagh ◽  
Dongyun Zhang ◽  
Abdul Zahid ◽  
Marvin Bergsneider ◽  
...  

Abstract Objective We evaluated tumor recurrence and regrowth rates following endoscopic transnasal transsphenoidal (TNTS) surgical removal in a consecutive series of clinically nonfunctioning pituitary adenomas (CNFTs). Design Retrospective chart review of clinical, biochemical, and sellar MRI findings in all TNTS surgeries in patients with CNFT, performed by a single surgeon, between 2008 and 2015 (n = 280). Patients Ninety-three patients met eligibility criteria, with complete clinical, biochemical, and imaging follow-up for a 3-year minimum. Results Of 85 patients who were not irradiated, 3-month postsurgical MRI demonstrated no residual tumor in 58 of 85 (68.2%), equivocal findings in 12 of 85 (14.1%), and definite residual tumor in 15 of 85 (17.6%) patients. Six of 85 (7.1%) demonstrated tumor regrowth by 3 years, and 2 further patients demonstrated true tumor recurrence at 3 and 6 years after surgery, respectively, for a total recurrence rate of 9.4% (8 of 85). Eight of the 93 patients were irradiated between 3 months and 4 years after pituitary surgery. In 3 patients with tumor regrowth, 2 exhibited residual tumor and 1 had no residual findings at the 3-month postoperative imaging. Overall, Ki-67 labeling index or Knosp grading did not predict recurrence. Conclusion Tumor recurrence at 3 years was low (1 of 58; 1.7%) if the 3-month postoperative MRI showed no residual tumor. The findings support a less frequent imaging schedule for this group. Patients with definite residual tumor visible at 3 months harbor the greatest risk for tumor growth, but regrowth does not occur in all patients (6 of 15; 40%).


2018 ◽  
Vol 80 (03) ◽  
pp. 287-294 ◽  
Author(s):  
Jose Gabrielle Matias ◽  
Ignacio Jusue-Torres ◽  
Brendan Martin ◽  
Ankush Bajaj ◽  
Ewa Borys ◽  
...  

Objectives Assess impact of Ki-67 labeling index (LI; Ki-67 LI) on risk of recurrence or progression of WHO grade I meningiomas. Study Design Retrospective study of adult patients who underwent resection of cranial base meningioma between 2004 and 2016. Results 272 patients fulfilled criteria for inclusion in the study. Average age was 61.8 years; 196 (72%) were females. Simpson's grade 1 resection was noted in 77 patients (32%), grade 2 in 39 (16%), grade 3 in 36 (15%), and grade 4 in 88 (37%). The Ki-67 LI was low (1–4%) in 214 (78.7%), intermediate (5–9%) in 44 (16.2%), and high (>10%) in 14 (5.2%). Median follow-up was 39 months (IQR: 16–71 months); 221 (87.1%) tumors remained stable or did not recur, 19 (7.4%) recurred, and 14 (5.5%) progressed. Compared with tumors with low Ki-67 LI, those with intermediate Ki-67 LI had 2.47 times (2.47 [1.09–5.59], p = 0.03), and those with high Ki-67 LI had 3.38 times (3.38 [1.16–9.89], p = 0.03) higher risk of recurrence or progression. Tumors with Ki-67 LI > 4% had a shorter time to recurrence or progression (p = 0.01). Recurrence or progression-free survival rates at 3, 5, and 10 years for tumors with low Ki-67 LI were 95%, 89%, and 75%, respectively; tumors with intermediate Ki-67 LI, 87%, 69%, and 52%, respectively; tumors with high Ki-67 LI, 78%, 49%, and 49%, respectively. Conclusions Following surgical resection of a WHO grade I cranial base meningioma, Ki-67 LI > 4% may predict an increased risk of recurrence or progression of residual tumor.


2019 ◽  
Vol 11 ◽  
pp. 175628721983777
Author(s):  
Ricardo G. Alvim ◽  
Christopher Hughes ◽  
Alexander Somma ◽  
Karan K. Nagar ◽  
Nathan C. Wong ◽  
...  

Objective: The objective of this study was to examine the impact of dehydrated human amnion/chorion membrane (dHACM) allografts on prostate and bladder cancer growth in the setting of residual disease and positive surgical margins. Materials and methods: A commercially available version of dHACM was used. Cytokines were identified and quantified, followed by comparative analysis of cell growth in two different human cell lines: prostate cancer (LNCaP) and bladder cancer (UM-UC-3), in vitro and in vivo. Tumor growth between the two groups, membrane versus no membrane implant, was compared and immunohistochemistry studies were conducted to quantify CD-31, Ki-67, and vimentin. A Student’s unpaired t-test was used to determine statistical significance. Results: The UM-UC-3 and LNCaP cells grew quicker in medium plus 10% serum and dHACM extract than in the other media ( p = 0.03). A total of 28 distinct cytokines were found in the extract, 11 of which had relatively high concentrations and are associated with prostate and bladder cancer tumor progression. In vivo LNCaP model, after 10 weeks, the median tumor volume in the membrane group was almost threefold larger than the partial resection alone ( p = 0.01). Two weeks after resection, in the UM-UC-3 model, the membrane group reached fourfold larger than the partial resection without membrane group ( p < 0.01). In both groups, the expression of CD-31 and Ki-67 markers were similar and showed no statistical significance ( p > 0.05). It was only in the LNCaP tumors that vimentin expression was significantly higher in the group without membrane compared with the membrane group ( p = 0.008). Conclusion: The use of dHACM after partial tumor resection is related to faster tumor relapse and growth in prostate and urothelial cancer in vivo models, showing a potential risk of rapid local recurrence in patients at high risk of positive margins.


2019 ◽  
Vol 161 (6) ◽  
pp. 1149-1156 ◽  
Author(s):  
Florian Grimm ◽  
Roland Maurus ◽  
Rudi Beschorner ◽  
Georgios Naros ◽  
Milan Stanojevic ◽  
...  

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