REST及其剪切变体REST4在肿瘤中的研究进展

抑制元素l-沉默转录因子(repressor element 1-silencing transcription factor,REST)又称为神经元限制性沉默因子(neuron-restrictive silencer factor,NRSF),是神经元特异性表达的负向调控因子,存在广泛的选择性剪切现象。REST及其剪切变体REST4在不同类型肿瘤中发挥重要作用,在胶质瘤、髓母细胞瘤等神经性肿瘤中REST可作为致癌因子,而在结肠癌、肺癌、乳腺癌等上皮性肿瘤中REST作为抑癌因子发挥肿瘤抑制作用。本文就REST及其剪切变体REST4在肿瘤中的研究进行综述。

Neuroendocrine tumors of the gastro-entero-pancreatic system

Gastro-entero-pancreatic (GEP) neuroendocrine tumors (NETs) are rare neoplasms, although their prevalence has increased substantially over the past three decades. Moreover, there has been an increased clinical recognition and characterization of these neoplasms. They show extremely variable biological behavior and clinical course. Most NETs have endocrine function and secrete peptides and neuroamines that cause distinct clinical syndromes, including carcinoid syndrome; however, many are clinically silent until late presentation with mass effects. Investigation and management should be individualized for each patient, taking into account the likely natural history of the tumor and general health of the patient. Management strategies include surgery for cure or palliation, and a variety of other cytoreductive techniques, and medical treatment including chemotherapy, and biotherapy to control symptoms due to hormone release and tumor growth, with somatostatin analogues (SSAs) and alphainterferon. New biological agents and somatostatintagged radionuclides are under investigation. Advances in the therapy and development of centers of excellence which coordinate multicenter studies, are needed to improve diagnosis, treatment and therefore survival of patients with GEP NETs.

Science Letters:Serum protein fingerprinting coupled with artificial neural network distinguishes glioma from healthy population or brain benign tumor

To screen and evaluate protein biomarkers for the detection of gliomas (Astrocytoma grade Ⅰ-Ⅳ) from healthy individuals and gliomas from brain benign tumors by using surface enhanced laser desorption/ionization time of flight mass spectrometry (SELDI-TOF-MS) coupled with an artificial neural network (ANN) algorithm. SELDI-TOF-MS protein fingerprinting of serum from 105 brain tumor patients and healthy individuals, included 28 patients with glioma (Astrocytoma Ⅰ-Ⅳ), 37 patients with brain benign tumor, and 40 age-matched healthy individuals. Two thirds of the total samples of every compared pair as training set were used to set up discriminating patterns, and one third of total samples of every compared pair as test set were used to cross-validate; simultaneously, discriminate-cluster analysis derived SPSS 10.0 software was used to compare Astrocytoma grade Ⅰ-Ⅱ with grade Ⅲ-Ⅳ ones. An accuracy of 95.7%, sensitivity of 88.9%, specificity of 100%, positive predictive value of 90% and negative predictive value of 100% were obtained in a blinded test set comparing gliomas patients with healthy individuals; an accuracy of 86.4%, sensitivity of 88.9%, specificity of 84.6%, positive predictive value of 90% and negative predictive value of 85.7% were obtained when patient's gliomas was compared with benign brain tumor. Total accuracy of 85.7%, accuracy of grade Ⅰ-Ⅱ Astrocytoma was 86.7%, accuracy ofⅢ-Ⅳ Astrocytoma was 84.6% were obtained when grade Ⅰ-Ⅱ Astrocytoma was compared with grade Ⅲ-Ⅳ ones (discriminant analysis). SELDI-TOF-MS combined with bioinformatics tools, could greatly facilitate the discovery of better biomarkers. The high sensitivity and specificity achieved by the use of selected biomarkers showed great potential application for the discrimination of gliomas patients from healthy individuals and glioma from brain benign tumors.

Three cases of retroperitoneal schwannoma diagnosed by EUS-FNA

Schwannomas are peripheral nerve tumors that are typically solitary and benign.Their diagnosis is largely based on surgically resected specimens.Recently,a number of case reports have indicated that retroperitoneal schwannomas could be diagnosed with endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA).We report the diagnosis of three cases of schwannoma using EUS-FNA.Subjects were two males and one female,ages 22,40,and 46 years,respectively,all of whom were symptom-free.Imaging findings showed well-circumscribed round tumors.However,as the tumors could not be diagnosed using these findings alone,EUS-FNA was performed.Hematoxylin-eosin staining of the resulting tissue fragments revealed bland spindle cells with nuclear palisading.There was no disparity in nuclear sizes.Immunostaining revealed S-100 protein positivity and all cases were diagnosed as schwannomas.Ki-67 indexes were 3%-15%,2%-3%,and 3%,respectively.No case showed any signs of malignancy.As most schwannomas are benign tumors and seldom become malignant,we observed these patients without therapy.All tumors demonstrated no enlargement and no change in characteristics.Schwannomas are almost always benign and can be observed following diagnosis by EUS-FNA.

Expression of FOXG1 is associated with the malignancy of human glioma

Objective： Recent evidence indicates that the increased expression of FOXG1 is associated with tumor genesis. This study was designed to explore the expression and role which FOXG1 plays in human glioma. Methods： We detected the expression of FOXG1 by immunohistochemistry in glioma tissue samples. Following the down-regulation of FOXG1 in glioma cell lines by a specific short hairpin RNA, the function of FOXG1 in proliferation and apoptosis was assessed. Results： Glioma tissues exhibited notably higher expression of FOXG1 compared with control brain tissues and was positively corre- lated with histological malignancy. The down-regulation of FOXG1 in glioma cells led to a cell apoptosis in vitro. Cenclusion： The overexpression of FOXG1 is a novel glioma malignancy marker, and FOXG1 may be used as a new target in therapeutic strategies for human glioma.

Brain metastases from hepatocellular carcinoma after hepatectomy

Hepatocellular carcinoma is a highly malignant neoplasm and frequently involves extrahepatic organs but decidedly rarely occurs in brain. We describe 3 cases of brain metastases in patients suffering from post-HBV hepatocarcinoma. The ＂stroke-like＂ presentation of the cerebral localization of the disease can be explained by both the important vascularization of the tumor and the frequent hemocoagulative alterations caused by the cirrhosis. The importance of diagnostic neuroradiology is briefly addressed, with reference to the fundamental role played by MRI. Surgery of these lesions does not present any particular technical problems as long as they are located in accessible areas and the patient＇s general and neurological conditions allow it. Postoperative radiotherapy seems to improve the quality and quantity of residual life, although the number of patients described in the literature was too small to draw any definite conclusion in this regard.

DIAGNOSIS AND TREATMENT OF MEDIASTINAL NEUROGENIC TUMORS--REPORT OF 110 CASES

Object.To study the clinical manifestations,diagnostic methods,surgical management ,and prognosis of various neurogenic mediastinal tumors.Method.One hundred and ten cases of neurogenic tumors of mediastinum were reviewed and retro-spectively analyzed.Results.Operative or hospitalization death happened in2cases,complications occurred in8cases,mostly were Horner’s syndrome or recurrent nerve paralysis.During the follow?up,there were2recur-rences in102benign tumors,and4cases of neurofibrosarcoma or malignant neurilemmoma died within3years postoperatively.Conclusion.Most mediastinal neurogenic tumors are benign.It is enough to establish diagnosis by chest X?ray and CT scan.There are different features in the clinical manifestations,diagnosing methods,and surgical management for the dumbbell tumors.Minimal invasive surgery and video?assisted thora-coscopy surgery(VATS)have a special value in treatment of the selected neurogenic mediastinal tumors.Benign neurogenic tumors rarely recur after complete resection,whereas malignant neurogenic tumors have poor prognosis.

Clinicopathological analysis of paraganglioma with literature review

AIM： To investigate the 152 cases of paragangliomas resected over the past 32 years in West China Hospital dinicopathologically.METHODS： All cases of paragangliomas diagnosed at the Department of Gastrointestinal Surgery and Department of Pathology, West China Hospital, China were reviewed. The pathological documents were supplied by the Department of Pathology, West China Hospital, and other necessary data were extracted from the hospital records. The statistical analyses were performed by survival analysis （Kaplan-Meier method）, descriptive statistical analyses and Х^2 analysis.RESULTS： The neuroendocrine marker vimentin was found to be selectively expressed in the benign tumors, and there were significant differences in the expression of those markers in both benign and malignant tumors. The survival analysis revealed that survival correlated significantly with the malignancy, metastasis and nodal status.CONCLUSION： Vimentin may be useful in the differential diagnosis between malignant and benign tumors. The difference in the expression of this marker in the tumors could be a clue to the future clinical diagnosis. The malignancy, metastasis and the nodal status may predict the prognosis of this disease.

PROGNOSTIC FACTORS FOR DEEP SITUATED MALIGNANT GLIOMAS TREATED WITH LINAC RADIOSURGERY

Objective To study the function of radiosurgery on malignant glioma by analyzing prognostic factors affecting malignant gliomas treated with linac radiosurgery. Method Fifty-eight patients with deep situated malignant gliomas, aged 7 to 70 years, 28 anaplastic astrocytomas and 30 glioblastomas multiforme were analyzed. The median volume of tumor was 10.67 cm3, and median prescription dose for linac radiosurgery was 20 Gy. Results were analyzed with Kaplan-Meier curve and Cox regression. Result In follow-up 44.8 percent tumors (26 patients) decreased in size. Median tumor local control interval was 10 months, 15 months for anaplastic astrocytomas, and 9 months for glioblastoma multiforme. Tumor local control probability was 37.9 percent for 1 year and 10.3 percent for 2 years. Median survival was 22.5 months for anaplastic astrocytoma, 13 months for glioblastoma multiforme, and 15 months for all patients. The survival probability was 79.3 percent at 1 year and 20.6 per-cent at 2 years. Isocenter numbers and tumor volume were the prognostic factors for tumor control, but conformity index was the prognostic factor for survival by Cox regression analysis. Considering pathology, only isocenter number and target volume significantly affected tumor control interval. Complications appeared in 44.8 percent patients and the median interval of com-plication onset was 8 months. Symptomatic cerebral edema was observed in 31.0 percent patients. Conclusion Linac radiosurgery can effectively improve tumor local control and prolong survival for deep situated mali-gnant gliomas.

Peripheral primitive neuroectodermal tumor of the posterior mediastinum: A case report

Peripheral primitive neuroectodermal tumor(pPNET) is an extremely rare disease entity of malignant tumors belonging to the Ewing sarcoma family that usually occurs in children and adolescents. We describe a 41-year-old female who presented with right upper abdominal pain. Surgical resection and biopsy revealed small round-cell tumor. Combined with immunohistochemical analysis, pPNET was diagnosed. No evidence of recurrence was noted at 18 months postoperatively. Even thought pPNET is a highly malignant tumor, Wide tumor-free resection and multi-agent chemotherapy can also obtain good clinical outcomes.

Capecitabine plus cisplatin treatment in patients with advanced hepatocellular carcinoma

Objective： Hepatocellular carcinoma （HCC） is the sixth most common cancer in the world and the third leading cause of cancer related death globally. Parentral treatment of Egyptian patients of bilharziasis contributed to the high incidence of viral hepatitis, and subsequently liver cirrhosis and HCC. CapecJtabJne plus cJsplatJn protocol was evaluated regarding the efficacy and safety in patients with advanced HCC as first line chemotherapy. Methods： One hundred patients with advanced HCC were randomized to receive either capecitabine （1000 mg/m2） twice daily for fourteen days plus intravenous cisplatin （60 mg/m2） on day one to be repeated every three weeks with a maximum of six cycles or placebo （phase III trial）. Results： Baseline characteristics were comparable in both groups. According to Barcelona Clinic Liver Cancer Staging System, stage C was the most predominant （82% vs. 75%） in both groups. Median OS was 12 months versus 10 months in favor of the treated group （P value 〈 0.05）. Median TTP was significantly higher in the chemotherapy group （7 months vs. 4.5 months） as well as disease control rate （40% vs. 29%）, no patient had achieved complete response. Grade 3 toxicity was more pronounced in the treatment group, as regards vomiting and diarrhea （10% vs. 2%）, neurotoxicity （6% vs. 2%）, elevation of aminotransferase and bilirubin （9.8% vs. 4.9%）, hand and foot syndrome reaction was recorded only in chemotherapy group. Conclusion： Capecitabine plus cisplatin regimen showed modest antitumor activity with tolerable toxicity in patients with advanced HCC. Moreover, because of the significantly prolonged time to progression, we demand further attention to this convenient, outpatient, and economic profile based chemotherapy protocol.

Treatment of Breast Cancer Accompanied by POEMS Syndrome:A Case Report

POLYNEUROPATHY, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes （POEMS） syndrome is a rare paraneoplastic syndrome characterized by the presence of a monoclonal plasma cell disorder, peripheral neuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and typical skin abnormalities. The cause of POEMS syndrome is unknown.1 Although numerous cases with POEMS syndrome have been reported, the POEMS syndrome patients with malignant tumor were seldom reported. Here, we present a rare case with breast cancer accompanied by POEMS syndrome.

Traumatic Neuromas in Breast Cancer Patients after Mastectomy

OBJECTIVE Traumatic neuromas are rare benign lesions occurring post-mastectomy,which are usually suspected as tumour recurrences before excision biopsy.We report six cases presenting with palpable nodules post-mastectomy,to emphasize the differential diagnosis of traumatic neuroma from recurrent cancer.METHODS Six cases were reviewed.The age of patients ranged from 33 to 61 years.Nodular masses were found close to the mastectomy scar during follow-up over a period of 2.8 to 8 years.RESULTS In one patient three nodular masses were detected.Five patients had received chemotherapy,three of which had also received ra-diotherapy.Ultrasound examinations showed a well-circumscribed,homoge-neous,hypo-echoic subcutaneous nodular lesion in four cases,and a poorly defined hypo-echoic nodule with good conduction in two cases.No obvious distant metastases had been identified.Each patient underwent surgical excisional biopsy.All of nodules had a diameter less than 1 cm.Histopatho-logical examination showed proliferation of nerve fibre bundles,which were disordered,oriented and well circumscribed in fibro-adipose tissue.CONCLUSION It was concluded that all of the lesions were traumatic neuromas,independent from the initial tumor.Traumatic neuromas occur-ring in mastectomy scars are difficult to distinguish from a tumor recurrence.Although radiological evaluation of the mass with ultrasound is of value,the diagnosis can only be confirmed following a histopathological evaluation.

Pharmacological management of neuropathic pain in patients with vestibular schwannomas:Experience of the Atlantic Lateral Skull Base Clinic

Neuropathic pain is chronic pain generated by disorders of the peripheral and central nervous system, including skull base tumours. A skull base tumour can be any type of tumour that forms in the skull base, and this includes vestibular schwannomas which arise from the sheath of the inner ear vestibulocochlear nerve(eighth cranial nerve). Growth of the tumour, surgical resection, and/or stereotactic radiotherapy may result incompression and/or irritation of the fifth cranial nerve(trigeminal nerve) resulting in facial pain and/or numbness. Non-trigeminal afferent input may contribute to the wide constellation of symptoms seen in orofacial pain patients. The purpose of this report was to develop a decision tool to guide the recognition and treatment of neuropathic pain in this specialized population. Recommendations for treatment are based on evidence presented in Canadian and international neuropathic treatment guidelines. Algorithms are included for assessment and treatment of adult patients with agents that are recognized to have analgesic efficacy within the broad context of neuropathic pain.

Role of F-18 FDG PET/CT imaging in the diagnosis of paraneoplastic neurological syndromes

Paraneoplastic neurological syndromes(PNS) is a series of rare neurologic disorders which happen with an underlying malignancy. It has various clinical symptoms proceding to the diagnosis of tumors. Although the abnormality of anti-neuronal antibodies is suggestive of PNS and tumors, there exist many false positive and false negative cases. The diagnosis of PNS is usually a challenge in clinic. Positron emission tomography/computed tomography(PET/CT) imaging is an anatomical and functional fusion imaging method, which provides the whole-body information by single scan. Fluorodeoxyglucose(FDG) PET/CT imaging can not only detect potential malignant lesions in the whole body, but also assess functional abnormality in the brain. In this review, the mechanism, clinical manifestation, diagnostic procedure and the recent progress of the utility of FDG PET/CT in PNS are introduced respectively.

Resection of the uncinate process of the pancreas due to a ganglioneuroma

A 33-year-old woman who presented with epigastric discomfort and diarrhea underwent an abdominal ultrasound(US).This investigation and subsequent contrastenhanced computed tomography,magnetic resonance imaging and endoscopic US with fine needle aspiration (FNA)revealed a 40 mm well-circumscribed mass in the uncinate process of the pancreas.Findings were suggestive of a mucinous or solid-cystic pseudopapillary tumor of the pancreas,although other lesions such as a nonfunctioning neuroendocrine tumor could not be ruled out.FNA samples were negative for malignant cells,but of limited value due to poor cellularity.It was decided to surgically remove the tumor because malignancy could not be discounted.Multiple intraoperative biopsies were suggestive of mesenchymal tumor and consequently a conservative resection(uncinatectomy)was performed. The postoperative course was uneventful.The definitive diagnosis was ganglioneuroma.Immunocytochemistry showed positive staining with vimentin,S-100 protein, neurofilament and neuron-specific enolase.Ganglioneuroma is a rare benign tumor that can also present as a pancreatic tumor.Uncinatectomy is feasible,safe and a good surgical technique for the treatment of nonmalignant tumors located in the uncinate process of the pancreas.

Peripheral primitive neuroectodermal tumors:a rare case report

We aimed to explore the diagnosis and treatment of peripheral primitive neuroectodermal tumors （pPNETs）. We retrospectively analyzed the diagnosis and treatment process of a patient who was diagnosed with pPNETs by pathology. This case was a man with soft masses arising from the left chest wall near the armpit and left supraclavicular of a 47-year-old man. The patient mainly presented with the masses which increasing gradually with obvious pain. Needle biopsy showed that they were both metastatic adenocaroinoma. Ultrasonography B revealed blood flow of these two low density placeholders can be seen in the signal, not oppression axillary and vein. Radical resection of the masses were performed. Histopathologic study and immunohistochemistry （IHC） confirmed the masses to be peripheral primitive neuroectodermal tumors, pPNETs is a rare malignant small round cell tumor. CT and MRI examination can estimate the resectability of the tumor; Ultrasound B can make sure its inside blood supply and the positional relationship between the mass and the surrounding vasculature. The diagnosis of pPNETs is based primarily on histopathologic study and IHC, especially those with the characteristics of the Homer-Wright and neuroendocrine markers. Radical resection of the tumor is the most effective therapeutic method. The effect of adjuvant chemo-radiation is worth affirmation. Autologous stem cell rescue besides adjuvant chemotherapy has been associated with prolonged survival.

Simultaneous large cell neuroendocrine carcinoma and adenocarcinoma of the stomach

A large cell neuroendocrine carcinoma(LCNEC) of the stomach is very rare.A 76-year-old Japanese man was admitted to our hospital because of epigastralgia and nausea.Endoscopy revealed 2 large tumors in the stomach.He did not have multiple endocrine neoplasia typeⅠor Zollinger-Ellison syndrome.Imaging modalities,including computed tomography and magnetic resonance imaging,revealed no other tumors.Gastrectomy,cholecystectomy,and lymph node dissection were performed.The resected stomach had 2 tumors:one was an antral ulcerated type 3 tumor measuring 5 cm x 5 cm,and the other was a polypoid type 1 tumor measuring 6 cm x 6 cm x 3 cm in the fundus.Microscopically,the antral ulcerated tumor was a well differentiated adenocarcinoma with deep invasion.The fundus polypoid tumor was a LCNEC,being composed of malignant large cells arranged in trabecular and nested patterns.The tumor cells were large and the nuclei were vesicular.Nucleoli were frequently present,and there were many mitotic figures,apoptotic bodies,and necrotic areas.Much lymphovascular permeation was seen.Seven out of 29 dissected lymph nodes showed metastatic foci;6 were from the LCNEC and 1 from theadenocarcinoma.Many intravascular tumor emboli of LCNEC were seen in the peritoneum around the lymph nodes.Mucins were present in the adenocarcinoma but not in the LCNEC.Immunohistochemically,the LCNEC tumor cells were positive for pancytokeratins,synaptophysin(50%positive) ,chromogranin A(10% positive) ,Ki-67(90%labeled) ,and platelet-derived growth factor-α(80%positive) .They were negative for KIT,p53,CD56,and neuron-specific enolase.The non-cancerous stomach showed a normal number of endocrine cells.The patient is now treated with adjuvant chemotherapy.

Non-specific histological variant of dysembryoplastic neuroepithelial tumor:a diagnostic challenge

Objective The accurate diagnosis of the non-specific variant of dysembryoplastic neuroepithelial tumor （DNT） is very difficult because it is characterized by absence of the histological hallmark of the ＂specific glioneuronal element＂ in lesions. We herein present two cases of the non-specific form of DNT to analyze the clinical, radiological, and histological features of this unusual subtype of DNT. Methods A 16-year-old and a 23-year-old patient had been treated for pharmacoresistant epilepsy for several years before undergoing referral to the hospital for further examination and treatment. Magnetic resonance imaging （MRI） revealed that both patients had a small, well-demarcated cystic lesion within the cortex of the brain without obvious contrast enhancement or peritumoral edema. The lesions were totally resected and routinely examined using histological and immunohistochemical analysis. Results Both lesions exhibited similar histological appearances with cyst formation and mural nodule architecture. The glial nodules were mainly composed of oligodendrocyte-like components, and partly of pi^oid cells resembling pilocytic astrocytoma. The cortex adjacent to the lesion in both cases was found to have the histological features of focal cortical dysplasia （FCD） Type I. Immunohistochemically, the oligoden- drocyte-like components were diffusely positive for Syn and Olig-2, but staining for CD34, p53, and IDH1 R132H was negative. The Ki-67 （MIB-1） labeling index was low, approximately 1%. There was no 1p/19q co-deletion in either lesion by fluorescence in situ hybridization （FISH） assay. Neither patient received postoperative adjuvant treatment, and both underwent regular follow-up for at least 24 months. No signs of recurrence or epileptic attacks were observed during the follow-up period. Conclusion The non-specific variant of DNT is a diagnostic challenge for pathologists in clinical practice, and differentiation from some low-grade gliomas needs to be considered. The careful inspection of radio- logic and histopathologic findings, accompanied by analysis of patients＇ clinical manifestations, may be helpful in making an accurate diagnosis.

Composite neuroendocrine and adenomatous carcinoma of the papilla of Vater

Malignant tumors of papilla are usually adenocarcinomas. We present a 67-year-old female who became icteric as result of a malignant tumor infiltrating the papilla of Vater. Histopathological assessment of surgically excised tumor showed both neuroendocrine and adenocarcinomatous features. To our knowledge, this is the seventh report of this rare neoplastic association in the duodenal periampullary region.