Hepatocellular carcinoma metastasis to the brain mimicking primary pituitary tumor around the sella turcica.

Aggressive pituitary neuroendocrine tumors (PitNETs)/adenomas are characterized by progressive growth despite surgery and all standard medical therapies and radiotherapy. A subset will metastasize to the brain and/or distant locations and are termed metastatic PitNETs (pituitary carcinomas). Studies of potential prognostic markers have been limited due to the rarity of these tumors. A few recurrent somatic mutations have been identified, and epigenetic alterations and chromosomal rearrangements have not been explored in larger cohorts of aggressive and metastatic PitNETs. In this study, we performed genome-wide methylation analysis, including copy-number variation (CNV) calculations, on tumor tissue specimens from a large international cohort of 64 patients with aggressive (48) and metastatic (16) pituitary tumors. Twelve patients with non-invasive pituitary tumors (Knosp 0–2) exhibiting an indolent course over a 5 year follow-up served as controls. In an unsupervised hierarchical cluster analysis, aggressive/metastatic PitNETs clustered separately from benign pituitary tumors, and, when only specimens from the first surgery were analyzed, three separate clusters were identified: aggressive, metastatic, and benign PitNETs. Numerous CNV events affecting chromosomal arms and whole chromosomes were frequent in aggressive and metastatic, whereas benign tumors had normal chromosomal copy numbers with only few alterations. Genome-wide methylation analysis revealed different CNV profiles and a clear separation between aggressive/metastatic and benign pituitary tumors, potentially providing biomarkers for identification of these tumors with a worse prognosis at the time of first surgery. The data may refine follow-up routines and contribute to the timely introduction of adjuvant therapy in patients harboring, or at risk of developing, aggressive or metastatic pituitary tumors.

We present an extremely rare case of lung cancer that metastasized to a gonadotroph pituitary neuroendocrine tumor, along with other organs. A 73-year-old man presented with dysarthria and bitemporal hemianopia. Head magnetic resonance imaging revealed cerebellar infarction and a pituitary tumor. Endoscopic transnasal pituitary tumor resection was performed. Pathologically, the tumor consisted of a well-differentiated neuroendocrine component, suggestive of a pituitary neuroendocrine tumor, alongside a poorly differentiated, highly malignant tumor with invasive growth. One month postoperatively, gadolinium-enhanced head magnetic resonance imaging revealed rapid growth of the residual tumor. Whole-body computed tomography and positron emission tomography revealed a 10-mm lung tumor and multiple muscle and bone metastases. Pathological examination of the pituitary tumor revealed poorly differentiated malignant cells. It was initially hypothesized that the pituitary neuroendocrine tumor had undergone malignant transformation with systemic metastases. However, further pathological examinations revealed steroidogenic factor 1-positive differentiated cells and steroidogenic factor 1-negative, synaptophysin-negative, cytokeratin-7-positive, and thyroid transcription factor-1-positive poorly differentiated malignant cells. The final diagnosis classified the tumor as a poorly differentiated lung adenocarcinoma that had metastasized to a gonadotroph pituitary neuroendocrine tumor, which showed rapid growth. Radiation and chemotherapy were administered; however, the patient died 6 months after surgery. Tumor metastasis to a pituitary neuroendocrine tumor is typically seen in older adults with non-functioning pituitary neuroendocrine tumors and no diabetes insipidus. Hence, clinicians should consider both metastatic pituitary neuroendocrine tumors and tumor metastasis to a pituitary neuroendocrine tumor when diagnosing a rapidly growing pituitary tumor in patients with signs of systemic metastasis.

Most pituitary incidentalomas are adenomas. They are classified as microadenoma (＜ 10 mm), macroadenoma (＞ 10 mm) and giant pituitary adenoma (＞ 40 mm). Invasive pituitary adenoma means the surrounding structures are invaded. We present an incidentally found hypermetabolic lesion at sphenoid sinus with the upper portion extending into pituitary fossa during F-18 FDG PET/CT imaging in an asymptomatic 70 year-old female with history of uterine endometrioid adenocarcinoma. MRI revealed the tumor epicenter at sphenoid sinus and normal pituitary gland was displaced laterally. The differential diagnosis included ectopic sphenoid sinus pituitary adenoma (with normal anterior pituitary gland), pituitary adenoma with atypical manifestation, primary tumor arising from sphenoid sinus (e.g., neuroendocrine tumor), chordoma, and metastasis, etc. Pathology revealed pituitary adenoma after Trans-sphenoidal resection.

Malignant melanomas arising from the sella turcica or sphenoidal sinus with bilateral invasion of the base of the skull or cavernous sinus are extremely rare. Whether the sella turcica or sphenoidal sinus is the site of origin is difficult to determine based on neuroradiological findings. An 83-year-old Japanese female presented with headache as the initial symptom. She suffered rapid progression of bilateral obstruction of the nasal cavity, left nasal bleeding, and bilateral visual field defects. The preoperative diagnosis was pituitary adenoma, metastatic tumor, or malignant paranasal tumor. Biopsy was performed. The histological diagnosis was malignant melanoma. Postoperatively, the tumor progressed rapidly. She suffered several cranial nerve pareses and hypopituitarism. She died within 6 months. Tumors arising from the sphenoidal sinus cause obstruction of the nasal cavity or nasal bleeding first, and then cause cranial nerve pareses by invasion of the cavernous sinus. This sequence of clinical manifestations can be attributed to the anatomical relationships between the sphenoidal sinus, nasal cavity, and cavernous sinus. Differential diagnosis of the origin in the sella turcica or sphenoidal sinus appears to be relatively easy based on further observation of the clinical course and symptoms.

Pituitary Apoplexy and CABG: Should We Change Our Strategy?

Epidemiology of hepatocellular carcinoma in the United States: where are we? Where do we go?

Most cases of hepatocellular carcinoma (HCC) are associated with cirrhosis related to chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Changes in the time trends of HCC and most variations in its age-, sex-, and race-specific rates among different regions are likely to be related to differences in hepatitis viruses that are most prevalent in a population, the timing of their spread, and the ages of the individuals the viruses infect. Environmental, host genetic, and viral factors can affect the risk of HCC in individuals with HBV or HCV infection. This review summarizes the risk factors for HCC among HBV- or HCV-infected individuals, based on findings from epidemiologic studies and meta-analyses, as well as determinants of patient outcome and the HCC disease burden, globally and in the United States.

Objective To investigate the related influence factors of the main extended direction of the pituitary macroadenoma in the vertical direction. Methods Clinical data of 184 pituitary macroadenoma patients were collected and analyzed retrospectively. The main extended direction in the vertical direction of the tumor was taken as the dependent variables. Patients were divided into two groups according to the suprasellar extension value of each tumor, (ie: suprasellar extension value>0 and suprasellar extension value≤0) . 10 selected indicators (age, sex, tumor type, diameter of diaphragmatic opening, sphenoid sinus type, sella type morphology, main sphenoid sinus septum bias, maximum width of sphenoid sinus septum, tumor cyst, number of longitudinal sphenoid sinus septum) were taken as independent variables and the factors which may influence the main extended direction were analyzed and selected by logistic regression method. Results Among the 184 patients, there were 121 cases extending mainly to the suprasellar direction, while the left cases extending mainly to the opposite direction. Statistical analysis showed the tumor type (P=0.026) , sphenoid sinus type (P=0.003) , sella type morphology (P=0.046) , diameter of diaphragmatic opening (P=0.003) and maximum width of the sphenoid sinus septum (P=0.009) were the independent predictors influencing the main expansion direction of pituitary macroadenomas in the vertical direction. Conclusions The pituitary macroadenoma is more likely to expand infrasellar in patients with sellar or sellaoccipital sphenoid sinus, sac sella turcica morphology, GH adenoma, smaller diaphragmatic opening diameter and narrower width of sphenoid sinus septum. The pituitary macroadenoma is more likely to expand suprasellar in patients with presellar sphenoid sinus, wok and cylinder sella turcica morphology, non-GH adenoma, larger diaphragmatic opening diameter and wider width of sphenoid sinus septum. Key words: Pituitary adenoma; Extended direction; Growth pattern; Sphenoid sinus; Sella turcica

POSTOPERATIVE neurologic or neuropsychologic deficits, or both, remain a common cause of disability after otherwise successful cardiac surgery. However, not all deficits are caused by gaseous or atheromatous emboli.

Complications Associated With Transsphenoidal Pituitary Surgery: Review of the Literature.

The incidence of hepatocellular carcinoma (HCC) in patients with a history of curatively-treated HCC is higher than in patients with no history of HCC even after sustained virologic response (SVR). To investigate differences in the patterns of HCC development after SVR in patients with a history of curatively-treated HCC and those with no history of HCC, based on gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI) findings. EOB-MRI was performed in 164 patients with HCV cirrhosis who achieved SVR by interferon-free direct-acting antiviral (DAA) therapy just before the start of therapy. Changes in EOB-MRI findings after SVR were compared prospectively between patients with (n = 62) and without (n = 102) a history of HCC. The incidence of HCC after SVR was higher in patients with a history of HCC (P < 0.0001). The prevalence of nonhypervascular hypointense nodules (NHHNs) by EOB-MRI was significantly higher in patients with a history of HCC at baseline (P = 0.05). Although there was no difference in the incidence of the hypervascularisation of baseline NHHNs to typical hypervascular HCC between patients with and without a history of HCC, the incidence of direct emergence of hypervascular HCC despite the absence of NHHNs at baseline was significantly higher in patients with a history of HCC (P < 0.0001). Direct emergence of hypervascular HCC and a higher prevalence of NHHNs before DD therapy contributed to the higher incidence of HCC after SVR. (UMIN000017020).

The study objective is to describe the removal of the pituitary adenoma from the posterior cranial fossa through endoscopic transsphenoidal trans-cavernous approach, when the main surgical corridor was the tumor-intact cavernous sinus. Materials and methods. A 55-year-old male patient with endosupraretrosellar endocrine-inactive pituitary adenoma was admitted to N.N. Burdenko Research Center of Neurosurgery. The patient had earlier undergone two surgeries for pituitary adenoma. Using the endoscopic endonasal transsphenoidal approach, we found that these surgeries resulted in the formation of scar-altered adipose tissue in the sphenoid sinus and partly in the sella turcica; anatomical landmarks indicating the midline and the location of the internal carotid arteries were absent. We formed an access to both retro- and suprasellar portions of the tumor between the sella turcica and cavernous segment of the internal carotid artery (through the cavernous sinus); then we dissected anterior and posterior walls of the sinus and revealed a soft capsule-free pituitary adenoma, which was completely removed by a vacuum aspirator. The skull base defect was repaired using the multilayer technique with autologous tissues. Results. After surgery, neurological status and visual functions did not change. In the postoperative period, we observed no oculomotor disorders, pituitary insufficiency, diabetes insipidus, or nasal liquorrhea. Follow-up computed tomography scans revealed no signs of intracranial complications or obvious residual tumor tissue. Magnetic resonance imaging 4 month postoperatively demonstrated small laterosellar fragments of the tumor in the sella turcica. The patient was further followed up. Conclusion. Cavernous sinus is a natural anatomical corridor providing access to the structures of the posterior cranial fossa and interpeduncular cistern. The main risk (damage to the cavernous segment of the internal carotid artery) can be minimized by using intraoperative dopplerography and visual control of all manipulations.

Recognizing the significant prevalence of hepatocellular carcinoma (HCC) in Saudi Arabia, and the difficulties often faced in early and accurate diagnoses, evidence-based management, and the need for appropriate referral of HCC patients, the Saudi Association for the Study of Liver diseases and Transplantation (SASLT) formed a multi-disciplinary task force to evaluate and update the previously published guidelines by the Saudi Gastroenterology Association. These guidelines were later reviewed, adopted and endorsed by the Saudi Oncology Society (SOS) as its official HCC guidelines as well. The committee assigned to revise the Saudi HCC guidelines was composed of hepatologists, oncologists, liver surgeons, transplant surgeons, and interventional radiologists. Two members of the task force served as guidelines editors. A wide based search on all published reports on all aspects of the epidemiology, natural history, risk factors, diagnosis, and management of HCC was performed. All available literature was critically examined and available evidence was then classified according to its strength. The whole document and the recommendations were then discussed in details by members and consensus was obtained. All recommendations in these guidelines were based on the best available evidence, but were tailored to the patients treated in Saudi Arabia. We hope that these guidelines will improve HCC patient care and enhance the multidisciplinary care needed for these patients.

The authors review the anatomy of the pituitary gland on the basis of cadaver dissection studies and anatomy of dural relationships of pituitary tumors and its extensions on the basis of a 35-year-old experience of surgically treating pituitary tumors. Perfect understanding of anatomical correlates and nuances of pituitary tumor surgery is essential to achieve satisfactory surgical results. The pituitary gland is located in a specially enclosed cavity that is neither intracranial nor extracranial. It is covered strategically by meninges. Pituitary gland has a close relationship with cavernous sinuses and sphenoid air sinus. Pituitary tumors range widely in their size. Whilst microadenomas are generally associated with hormonally active tumors, large and giant sized tumors are usually hormonally non-functional. Surgical issues are unique for all sizes of pituitary tumors. Giant pituitary tumors grow in size, but a majority of them are confined to dural compartmental space. Recently proposed classification schemes have enhanced the understanding of anatomical subtleties and dural relationships of growing and giant pituitary tumors.

To evaluate the real-world efficacy and safety of temozolomide (TMZ) in aggressive and metastatic pituitary neuroendocrine tumors in a Latin American setting, and to address whether TMZ achieves meaningful radiological and biochemical disease control with acceptable toxicity. We conducted a retrospective multicenter study across Brazilian reference centers including patients with aggressive/metastatic pituitary adenomas treated with TMZ and followed for ≥ 6 months. The radiological response was assessed via RECIST 1.1. For functioning pituitary adenomas, biochemical response was assessed using prespecified hormonal criteria. Adverse events were collected from medical records. Thirty patients were included (mean age 29.5 years; 53% female). All the tumors were macroadenomas, and 56% were giant (> 4 cm). Twenty-one pituitary adenomas were functioning and four were metastatic. Ki-67 was > 3% in 73% of the patients. The mean time from diagnosis to TMZ initiation was 102 months. The radiological disease control rate (partial response or stable disease) was 93.3%. Among functioning tumors, the biochemical disease control rate was 81.2%, with an objective biochemical response rate (complete + partial response) of 68.8%. Adverse events, most commonly nausea and myelotoxicity, occurred in 66% of patients. In this multicenter Brazilian real-world cohort, TMZ provided high radiological and biochemical disease control with an acceptable safety profile, suggesting that TMZ is the preferred first-line systemic chemotherapy for aggressive/metastatic pituitary adenomas after the failure of standard therapies.