Proliferation index of nonfunctioning pituitary adenomas: correlations with clinical characteristics and long-term follow-up results

OBJECTIVE: The recurrence of nonfunctioning pituitary adenomas (NFPAs) after surgical removal is common. The aim of our study was to investigate and correlate the growth fraction of NFPAs with clinical characteristics and long-term follow-up results. METHODS: Tumor specimens were obtained from 101 consecutive patients with NFPAs (48 female patients and 53 male patients; mean age, 52.0 +/- 1.5 yr). Specimens were immediately fixed in 10% buffered formalin and then embedded in paraffin. The Ki-67 antigen was assessed by immunocytochemical analysis using the monoclonal antibody MIB-1. The Ki-67 antigen labeling index (LI) was determined by counting a total of at least 1,000 neoplastic nuclei. RESULTS: The mean Ki-67 LI for the 101 patients was 2.4 +/- 0.3% (range, 0-23.0%). Only age at surgery was inversely correlated with the Ki-67 LI; sex, maximal tumor diameter, and invasiveness into the cavernous sinuses did not significantly affect the Ki-67 LI. The mean follow-up period was 39.7 +/- 2.1 months. During follow-up monitoring, 23 patients experienced tumor recurrence, after a mean period of 28.6 +/- 4.8 months. Invasiveness of the tumor on preoperative magnetic resonance imaging scans was the strongest predictor of late tumor recurrence, followed by previous pituitary surgery, younger age, and lack of postoperative radiotherapy. The Ki-67 LI had no independent prognostic value. CONCLUSION: Our study suggests that the clinical characteristics of patients with NFPAs, except for age at surgery, are not correlated with the Ki-67 LI. Moreover, the Ki-67 LI does not seem to provide independent information to identify patients at high risk for tumor recurrence.     

Lymphangioma of the spermatic cord

We report a new case of spermatic cord lymphangioma in a infant 2 years old. The initial diagnosis was funicular hydrocele. The treatment was the local excision of tumor and the diagnostic was histological. Postoperative course was excellent. Must be explored the transillumination of the mass which would have led us to think other the diagnosis different from that of the cord hydrocele before the operation since it would have given negative. During the operation, must the assured that the cystic anomaly is limited to spermatic cord, to evite recurrences in the postoperative course.     

Phase II study of preoperative radiotherapy and concomitant weekly intravenous oxaliplatin combined with oral capecitabine for stages II–III rectal cancer

Introduction

A prospective phase II study was conducted to assess the clinical activity and tolerability of oxaliplatin, capecitabine, and radiotherapy (RT) for neoadjuvant therapy of stages II?CIII rectal cancer.

Materials and methods

Patients with histologically confirmed stages II?CIII (T3?CT4 and/or N+) resectable rectal adenocarcinoma were eligible. Capecitabine was administered at 825?mg/m² twice daily for 5?days/week and oxaliplatin at 50?mg/m² on day 1 weekly for 5?weeks starting the first day of RT (before RT). RT consisted of a total dose of 45?Gy delivered in 25 fractions of 1.8?Gy, 5?days per week, for 5?weeks.

Results

A total of 46 patients were included (35 male, 10 female, median age 62?years). TNM Stage was T3 in 43 patients and T4 in 2. Twenty-eight patients had suspected nodal involvement. The intended chemoradiation treatment was completed in 94?% patients. Grade 3/4 toxicity included lymphocytopenia (6 patients), diarrhea (4 patients), emesis (2 patients), asthenia (3 patients), anorexia (1 patient), and hepatic toxicity (1 patient). Grade 1 neurotoxicity occurred in 18 patients, Grade 2 neurotoxicity in 3, and Grade 1 palmoplantar erythrodysesthesia in 2. Forty-two patients underwent surgery (complete resection 95?%, sphincter-saving operation 55?%). The overall pathologic response rate was 83?%, with a pathologic complete response (pCR) rate of 11.9?% (95?% CI 4.0?C25.6).

Conclusions

The pCR rate observed with oxaliplatin plus capecitabine and RT did not reach the pre-specified criteria of efficacy in this trial, which is in line with recent results of randomized phase III trials.     

Peripheral Angioplasty as the First-choice Revascularization Procedure in Diabetic Patients with Critical Limb Ischemia: Prospective Study of 993 Consecutive Patients Hospitalized and Followed Between 1999 and 2003

OBJECTIVE: To evaluate the effectiveness of peripheral angioplasty (PTA) as the first-choice revascularisation procedure in diabetic patients with critical limb ischemia (CLI). DESIGN: Prospective study. METHODS: PTA was employed as first choice revascularisation in a consecutive series of diabetic patients hospitalized for CLI between January 1999 and December 2003. RESULTS: PTA was successful performed in 993 patients. Seventeen (1.7%) major amputations were carried out. One death and 33 non-fatal complications were observed. Mean follow-up was 26+/-15 months. Clinical restenosis was observed in 87 patients. The 5 years primary patency was 88%, 95% CI 86-91%. During follow-up 119 (12.0%) patients died at a rate of 6.7% per year. CONCLUSIONS: PTA as the first choice revascularisation procedure is feasible, safe and effective for limb salvage in a high percentage of diabetic patients. Clinical restenosis was an infrequent event and PTA could successfully be repeated in most cases.     

Suprasellar granular cell tumor of the neurohypophysis: surgical outcome of a very rare tumor

Purpose

Granular cell tumors of the neurohypophysis are rare, solitary lesions, mostly presenting in the adult age. They rarely grow to a sufficient size to cause mass effect related symptoms and they may be found in most cases incidentally at autopsy. Because of their rarity as of now they have been described only as case reports or included in small clinical series.

Methods

We report a series of 11 patients, who underwent surgery for granular cell tumors of the neurohypophysis between 1996 and 2013 in a single center.

Results

Mean follow-up time after treatment was 92.2 months (range 9–231 months). Mean age at surgery was 40.7 years (range 12–66 years). There were 7 males (63.6 %) and 4 females (36.4 %). Main symptoms at presentation were: hyperprolactinemia (72.7 %), visual impairment (45.5 %) and headache (36 %). Except for 2 patients, all the others underwent surgery as primary treatment at our Institution, through a transsphenoidal (54.5 %) or a transcranial approach (45.5 %). Overall- and progression-free survival times for the entire series (calculated from the time of diagnosis) were 112.9 and 100.5 months respectively. There was one case of perioperative death in a patient who had undergone repeat transcranial surgery for residual tumor.

Conclusions

Although extremely rare, granular cell tumors of the neurohypophysis have to be considered in the differential diagnosis of suprasellar masses, to avoid misleading interpretation and consequent wrong therapeutic management. Early diagnosis, extensive tumor removal, opportune indication of adjuvant radiotherapy are the keys to manage these cases.

     

Identification of somatic gene mutations in penile squamous cell carcinoma

There is a lack of studies on somatic gene mutations and cell signaling driving penile carcinogenesis. Our objective was to analyze somatic mutations in genes downstream of EGFR in penile squamous cell carcinomas, especially the mTOR and RAS/MAPK pathways. We retrospectively analyzed somatic mutations in 10 in situ and 65 invasive penile squamous cell carcinomas by using Sequenom's Mass Spectrometry iPlex Technology and Oncocarta v1.0 Panel. The DNA was extracted from FFPE blocks and we identified somatic missense mutations in three in situ tumors and in 19 invasive tumors, mostly in PIK3CA, KRAS, HRAS, NRAS, and PDGFA genes. Somatic mutations in the PIK3CA gene or RAS family genes were neither associated with tumor grade, stage or outcome, and were equally often identified in hrHPV positive and in hrHPV negative tumors that showed no p53 expression. Mutations in PIK3CA, KRAS, and HRAS are frequent in penile squamous cell carcinoma and likely play a role in the development of p53‐negative tumors. Although the presence of these mutations does not seem to correlate with tumoral behavior or outcome, they could be biomarkers of treatment failure with anti‐EGFR mAb in patients with penile squamous cell carcinoma. © 2015 Wiley Periodicals, Inc.     

Vascular endothelial growth factor production and regulation in rodent and human pituitary tumor cells in vitro

Angiogenesis, the formation of a new blood supply, is an essential step in tumorigenesis. Although vascular endothelial growth factor (VEGF) is known to be a very potent angiogenic factor in most solid tumors, little is known about its production and regulation in pituitary adenomas. We have investigated basal and stimulated VEGF production by rodent pituitary tumor cells (mouse corticotrope AtT20, rat lactosomatotrope GH3, mouse gonadotrope alpha T3-1 and mouse folliculostellate TtT/GF cells), and by hormone-inactive (27), corticotrope (9), lactotrope (3) and somatotrope (21) human pituitary adenoma cell cultures. All 4 pituitary cell lines secreted VEGF, which in the case of AtT20, GH3 and TtT/GF cells was inhibited by approximately 50% by dexamethasone. TtT/GF cells were the most responsive to the different stimuli used since basal values were augmented by pituitary adenylate cyclase activating polypeptide-38 (PACAP-38), interleukin-6 (IL-6), transforming growth factor-alpha (TGF-alpha), IGF-I and the somatostatin analogue ocreotide. However, in GH3, AtT20 and alpha T3-1 cells, basal VEGF levels where not enhanced with any of the stimuli tested. The majority of the human adenomas tested (92%) basally secreted measurable VEGF which was inhibited by dexamethasone in most cases (84%). VEGF levels were increased in hormone inactive adenomas, somatotrope tumors and prolactinomas by TGF-alpha, PACAP-38, and 17 beta-estradiol, respectively. In conclusion, pituitary tumor cells are capable of producing VEGF which may be involved in tumoral angiogenesis. Our results concerning the suppression of VEGF by dexamethasone suggest that glucocorticoids may have anti-angiogenic properties and therefore therapeutic relevance for the treatment of pituitary adenomas.     

Theophylline blunts the GH-response to growth hormone releasing hormone in normal subjects

Theophylline enhances GH-secretion in vitro, whereas in vivo a slight decrease of basal GH-levels has been observed. In the present study the effect of theophylline on the GH-responsiveness to acute and continuous administration of growth hormone releasing hormone (GHRH) was investigated. The following protocol was performed. GHRH study. Fifty micrograms GHRH was given as an iv bolus followed by constant GHRH-infusion (100 micrograms/h) over 2 h after which another GHRH bolus of 50 micrograms was given. GHRH plus theophylline study. GHRH was administered as in the first study and theophylline was infused at a constant rate of 3.56 mg/min over 3 h, starting one h before the GHRH bolus. Theophylline study. Only saline and theophylline were infused. GHRH alone led to a GH-rise within 30 min with a maximum of 22.8 +/- 7.2 ng/ml (mean +/- SE) after which GH-levels decreased despite continuous GHRH-infusion to a nadir of 12.1 +/- 4.4 ng/ml at 105 min. The second GHRH bolus led to a minimal GH-increase (13.3 +/- 6.4 ng/ml at 135 min). Theophylline administration resulted in blunting of the GH-response to GHRH in all volunteers, with GH levels fluctuating between 4-6 ng/ml throughout GHRH-administration. Theophylline alone did not affect GH-levels in three subjects studied, whereas in the other one a GH secretory episode 90 min after administration of the drug was observed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Long-course temozolomide in aggressive pituitary adenoma: real-life experience in two tertiary care centers and review of the literature

Pituitary - Aggressive pituitary adenomas (APAs) and pituitary carcinomas (PCs) are challenging for their invasive nature, resistance to treatment and recurrences. Temozolomide (TMZ) is...