强心通脉胶囊对充血性心力衰竭大鼠血流动力学、神经内分泌和水通道蛋白-2的影响

目的探讨强心通脉胶囊对充血性心力衰竭(CHF)大鼠模型血流动力学、神经内分泌及肾脏水通道蛋白-2(AQP2)基因表达的影响。方法采用左冠状动脉结扎制备充血性心力衰竭大鼠模型,术后第6周观察大鼠的心功能变化,用放免法检测大鼠血浆心钠素(ANP)、内皮素(ET-1)水平;采用RT-PCR方法检测大鼠肾脏AQP2mRNA的表达。结果充血性心力衰竭大鼠血流动力学参数、ANP、ET-1、AQP2mRNA的表达较之假手术对照组明显异常,强心通脉胶囊可显著改善上述异常。结论左冠状动脉结扎所致的充血性心力衰竭大鼠,血流动力学参数、血浆ANP、ET-1和肾脏AQP2mRNA的表达异常,强心通脉胶囊对充血性心力衰竭的治疗作用与改善大鼠的血流动力学参数和降低血浆ANP、ET-1水平,并能部分纠正肾脏AQPmRNA的异常表达有关。

BIO-INSPIRED SELF-ADAPTIVE MANUFACTURING SYSTEM CONTROL ARCHITECTURE

Future manufacturing systems need to cope with frequent changes and disturbances, therefore their control architectures require constant adaptability, agility, stability, self-organization, intelligence, and robustness. Bio-inspired manufacturing system can well satisfy these requirements. For this purpose, by referencing the biological organization structure and the mechanism, a bio-inspired manufacturing cell is presented from a novel view, and then a bio-inspired self-adaptive manufacturing model is established based on the ultra-short feedback mechanism of the neuro-endocrine system. A hio-inspired self-adaptive manufacturing system coordinated model is also established based on the neuro-endocrine-immunity system （NEIS）. Finally, an example based on pheromone communication mechanism indicates that the robustness of the whole manufacturing system is improved by bio-inspired technologies.

Clinico-pathologic significance of neuroendocrine cells in gastric carcer tissue

AIMS To elucidate the biological and clinicopathological signifi- cance of neuroendocrine(NE)cells in gastric carcinoma(GC). METHODS One hundred and eighty-nine cases of various histo- logical types of GC were observed using light microscopy, histochemistry,immunohistochemistry and electron microscopy. Of them 127 patients were followed up. RESULTS Chromogranin A(CgA)positive GC was demonstrat- ed in 85 cases(45.0%).The typos of NE cells in GC were probed using 9 kinds of hormone antibodies 49 cases(67.2%) contained more than one hormone.NE cells were found more often in poorly differentiated GC than in well differentiated ones(P<0. 01).Expression of some kinds of hormone Was relative to the dif- ferentiation and histological types of GC.BOM,CT(P<0.01) GAST and 5-HT(P<0.05)were more expressed in poorly differ- entiated cases than in well defferentiated ones.Nineteen cases of the matastatic foci in regional lymph nodes were found to have CgA positive cancer cells.The presence of HCG in matastatic lymph nodes was more often observed than that of other hormone (P<0.01).The survival rate of patients with NE positive GC was 38.9% and negative GC 52.7%.Five of 7 patients(71. 4%)with somatostatin positive GC still survived at follow up of 33-66 months,but 4 patients with HCG positive GC died in 12-29 months. CONCLUSIONS The NE cells occur more frequently in poorly differentiated GC.Certain hormones appear to be related to the metastasis and prognosis.

Prognostic Significance of Neuroendocrine Differentiation in Non-small Cell Lung Cancer Patients' Survival

Objective： To observe the relationship between non-small cell lung cancer with neuroendrocrine differentiation （NSCLC-NE） and patients＇ postoperative survival. Methods： During April 1997 to April 1999, 98 cases of hlng cancer were surgically treated. The tumor specimens of the patients were stained by NE markers, i.e. neuron specific enolase （NSE） and synaptophysin （SY）. The intensity of NE markers reaction was divided as ＂＋＂. ＂＋＋＂. ＂＋＋＋＂ scale groups. The same specimens were also examined under an electron microscope for the specific neuroendocrine granules. All enrolled patients were followed up for 36 months, and the longest follow-up time was 60 months. The COX proportional hazard model multivariate analysis was applied to observe the relationship between the NSCLE-NE and the patients＇ postoperative survival. Results： In 91 cases of NSCLC, 63.7% （58/91） were positive for NE stain reaction. Among them, 59.3% （54/91） were positive for NSE and 24.1% （22/91） for SY. 48.4% （44/91） were considered as NSCLC-NE by the combination of NE inarker stain reaction and electron microscopic examination. COX proportional hazard model lnnltivariate analysis showed that the NSCLC-NE patients＇ survival was significantly shortened （P=0.048）. The following factors were related to NSCLC-NE patients＇ survival： lung cancer cell differentiation （P=0.006）, clinical lung cancer stage （P=0.001）, the NE markers reaction （P=0.054）. Conclusion： NSCLE-NE is significantly related to the cancer cell differentiation and the patients＇ postoperative survival. The NE markers should be applied clinically as one of prognostic factors to evaluate the postoperative survival of NSCLC patients.

Quantitative ultrastucture analysis of neuroendocrine cells of gastric mucosa on normal and pathological conditions

AIMS To study the quantitative ultrastucture of neu- roendocrine cells of gastric mucosa on normal anc pathological conditions including the duodenal ulcer (DU) and Zollinger-Ellison syndrome (ZES). METHODS The neuroendocrine cells of the gastric mucosa of eight normal subjects,six patients with DU and five patients with ZES were quantitatively investi- gated with electro microscope and ultrastructure image analyzer. RESULTS The volume density of neuroendocrine cells in DU was 1.3% and 0.8% (vs 1.6% and 0.9%,P>0.05) in gastric antrum and corpus respectively. In antrum,G cells was of 65% (P< 0.05),D cells decreased in cell density (3% vs 9.5%) and in number of cell per unit area (P<0.01). In corpus,the cell density of ECL cells increased (49% vs 30%,P<0.05);D cells and EC cells decreasec (2% P<0.01 and 4% P<0.05,respectively),and the number of D cell per unit area markedly decreased. In ZES,D cells in corpus decreased in cell density (4% vs 22%,P<0.01) and P cells also decreased (11% vs 24%,P<0.05). The density of ECL cells increased (65% vs 30%,P<0.01). CONCLUSIONS In DU and ZES,both the number and type of NE cells present some changes. Incresed gastrin in DU and ZES patients may be caused by the decrease of D cells and somatostatin secretion.

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.

Irritable bowel syndrome:Diagnosis and pathogenesis

Irritable bowel syndrome (IBS) is a common gastro-intestinal (GI) disorder that considerably reduces the quality of life. It further represents an economic burden on society due to the high consumption of healthcare resources and the non-productivity of IBS patients. The diagnosis of IBS is based on symptom assessment and the Rome Ⅲ criteria. A combination of the Rome Ⅲ criteria, a physical examination, blood tests, gastros-copy and colonoscopy with biopsies is believed to be necessary for diagnosis. Duodenal chromogranin A cell density is a promising biomarker for the diagnosis of IBS. The pathogenesis of IBS seems to be multifactorial, with the following factors playing a central role in the pathogenesis of IBS:heritability and genetics, dietary/intestinal microbiota, low-grade inflammation, and disturbances in the neuroendocrine system (NES) of the gut. One hypothesis proposes that the cause of IBS is an altered NES, which would cause abnormal GI motility, secretions and sensation. All of these abnormalities are characteristic of IBS. Alterations in the NES could be the result of one or more of the following:genetic factors, dietary intake, intestinal flora, or lowgrade inflammation. Post-infectious IBS (PI-IBS) and inflammatory bowel disease-associated IBS (IBD-IBS) represent a considerable subset of IBS cases. Patients with PI-and IBD-IBS exhibit low-grade mucosal inflammation, as well as abnormalities in the NES of the gut.

Nervous and Neuroendocrine regulation of the pathophysiology of cholestasis and of biliary carcinogenesis

Cholangiocytes, the epithelial cells lining the biliary ducts, are the target cells in several liver diseases. Cholangiopathies and cholangiocarcinoma generate interest in many scientists since the genesis. The developing mechanisms, and the therapeutic tools of these diseases are still undefined. Several studies demonstrate that many hormones, neuropeptides and neurotransmitters regulate malignant and non-malignant cholangiocyte pathophysiology in the course of chronic biliary diseases. The aim of this review is to present the findings of several studies published in the recent years that contributed to clarifying the role of nervous and neuroendocrine regulation of the pathophysiologic events associated with cholestasis and cholangiocarcinoma development. This manuscript is organized into two parts. The first part offers an overview of the innervation of the liver and the origin of neuroendocrine hormones, neurotransmitters and neuropeptides affecting cholangiocyte function and metabolism. The first section also reviews the effects played by several neuroendocrine hormones and nervous system on cholangiocyte growth, survival and functional activity in the course of cholestasis. In the second section, we summarize the results of some studies describing the role of nervous system and neuroendocrine hormones in the regulation of malignant cholangiocyte growth.

Surgicopathological classification of hepatic space-occupying lesions:A single-center experience with literature review

Accompanying rapid developments in hepatic surgery,the number of surgeries and identifications of histological types of primary hepatic space-occupying lesions (PHSOLs) have increased dramatically.This has led to many changes in the surgicopathological spectrum of PHSOLs,and has contributed to a theoretical basis for modern hepatic surgery and oncological pathology.Between 1982 and 2009 at the Eastern Hepatobiliary Surgery Hospital (EHBH) in Shanghai,31 901 patients underwent surgery and were diagnosed as having a PHSOL.In this paper,we present an analysis of the PHSOL cases at the EHBH for this time period,along with results from a systematic literature review.We describe a surgicopathological spectrum comprising more than 100 types of PHSOLs that can be stratified into three types:tumor-like,benign,and malignant.We also stratified the PHSOLs into six subtypes derived from hepatocytes;cholangiocytes;vascular,lymphoid and hemopoietic tissues;muscular,fibrous and adipose tissues;neural and neuroendocrine tissues;and miscellaneous tissues.The present study provides a new classification system that can be used as a current reference for clinicians and pathologists to make correct diagnoses and differential diagnoses among various PHSOLs.

Impact of Helicobacter pylori infection on ghrelin and various neuroendocrine hormones in plasma

AIM: Ghrelin, an endogenous ligand for growth hormone secretagogue receptor, influences appetite, energy balance, gastric motility and acid secretion. The stomach is the main source of circulating ghrelin. There are inconsistent reports on the influence of Helicobacter pylori (H pylori) infection on circulating ghrelin levels. We sought to elucidate the relationship between ghrelin and various peptides in plasma, with special reference to H pylori.METHODS: Plasma ghrelin levels were measured by radioimmunoassay in 89 subjects who were referred for upper gastrointestinal endoscopy, consisting of 42 H pylori infected and 47 uninfected ones. Plasma gastrin,somatostatin, leptin, insulin-like growth hormone 1 (IGF-1)and chromogranin A concentrations were also measured.Twelve patients were treated with anti- H pylori regimen.RESULTS: Ghrelin circulating levels were greatly decreased in H pylori-positive than negative individuals (194.2±90.2fmol/mL and 250.4±84.1 respectively, P＜0.05), but did not significantly alter following the cure of infection (176.5±79.5 vs 191.3±120.4). There was a significant negative correlation between circulating ghrelin and leptin levels, as well as body mass index, for the whole and uninfected population, but not in H pylori-infected patients. Plasma ghrelin concentrations correlated positively with IGF-1 in H pylori-negative group and negatively with chromogranin A in the infected group.There were no significant correlations among circulating levels of ghrelin, gastrin and somatostatin irrespective of H pylori status.CONCLUSION: H pylori infection influences plasma ghrelin dynamics and its interaction with diverse bioactive peptides involved in energy balance, growth and neuroendocrine function.

Endoscopic submucosal dissection for foregut neuroendocrine tumors:An initial study

AIM： To evaluate the feasibility and efficacy of endo- scopic submucosal dissection （ESD） for foregut neuro- endocrine tumors （NETs）. METHODS： From April 2008 to December 2010, pa- tients with confirmed histological diagnosis of foregut NETs were included. None had regional lymph node enlargement or distant metastases to the liver or lung on preoperative computerized tomography scanning or endoscopic ultrasonography （EUS）. ESD was attempted under general anesthesia. After making several mark-ing dots around the lesion, a mixture solution was injected into the submucosa. The mucosa was incised outside the marking dots. Dissection of the submu- cosal layer beneath the tumor was performed under direct vision to achieve complete en bloc resection of the specimen. Tumor features, clinicopathological char- acteristics, complete resection rate, and complications were evaluated. Foregut NETs were graded as G1, G2, or G3 on the basis of proliferative activity by mitotic count or Ki-67 index. All patients underwent regular follow-up to evaluate for any local recurrence or dis- tant metastasis. RESULTS： Those treated by ESD included 24 patients with 29 foregut NETs. The locations of the 29 lesions are as follows： esophagus （n = 1）, cardia （n = 1）, stomach （n = 23）, and duodenal bulb （n = 4）. All le- sions were found incidentally during routine upper gastrointestinal endoscopy for other indications, and none had symptoms of carcinoid syndrome. Preop- erative EUS showed that all tumors were confined to the submucosa. Among the 24 gastric lesions, 16 le- sions in 11 patients were type I gastric NETs arising in chronic atrophic gastritis with hypergastrinemia, while the other 8 solitary lesions were type Ⅲ because of absence of atrophic gastritis in these cases. All of the tumors were removed in an en bloc fashion. The av- erage maximum diameter of the lesions was 9.4 mm （range： 2-30 ram）, and the procedure time was 20.3 rain （range： 10-45 rain）. According to the World Health Organization 2010 classification, histological evaluation determined that 26 lesions were NET-G1, 2 gastric le- sions were NET-G2, and 1 esophageal lesion was neu- roendocrine carcinoma （NEC）. Complete resection was achieved in 28 lesions （28/29, 96.6%）, and all of them were confined to the submucosa in histopathologic assessment with no lymphovascular invasion. The re- maining patient with NEC underwent additional surgery because the resected specimens revealed angiolym- phatic and muscularis invasion, as well as incomplete resection. Delayed bleeding occurred in 1 case 3 d af- ter ESD, which was managed by endoscopic treatment. There were no procedure-related perforations. During a mean follow-up period of 24.4 mo （range： 12-48 too）, local recurrence occurred in only 1 patient 7 mo after initial ESD. This patient successfully underwent repeat ESD. Metastasis to lymph nodes or distal organs was not observed in any patient. No patients died dur- ing the study period. CONCLUSION： ESD appears to be a safe, feasible, and effective procedure for providing accurate histo- pathological evaluations and curative treatment for eligible foregut NETs.

Neuroendocrine carcinomas arising in ulcerative colitis:Coincidences or possible correlations?

Patients with inflammatory bowel disease （IBD） are at increased risk of colorectal malignancies. Adenocarcinoma is the commonest type of colorectal neoplasm associated with ulcerative colitis （UC） and Crohn＇s disease, but other types of epithelial and non-epithelial tumors have also been described in inflamed bowel. With regards to non-epithelial malignancies, lymphomas and sarcomas represent the largest group of tumors reported in association with IBD, especially in immunosuppressed patients. Carcinoids and in particular neuroendocrine neoplasms other than carcinoids （NENs） are rare tumors and are infrequently described in the setting of IBD. Thus, this association requires further investigation. We report two cases of neoplasms arising in mild left-sided UC with immuno- histochemical staining for neuroendocrine markers： a large cell and a small cell neuroendocrine carcinoma of the rectum. The two patients were different in age （35 years vs 77 years） and disease duration （11 years vs 27 years）, and both had never received immunosuppressant drugs. Although the patients underwent regular endoscopic and histological follow-up, the two neoplasms were locally advanced at diagnosis. One of the two patients developed multiple liver metastases and died 15 mo after diagnosis. These findings confirm the aggressiveness and the poor prognosis of NENs compared to colorectal adenocarcinoma. While carcinoids seem to be coincidentally associated with IBD, NENs may also arise in this setting. In fact, long-standing inflammation could be directly responsible for the development of pancellular dysplasia involving epithelial, goblet, Paneth and neuroendocrine cells. It has yet to be established which IBD patients have a higher risk of developing NENs.

Coexistence of small cell neuroendocrine carcinoma and villous adenoma in the ampulla of Vater

Small cell neuroendocrine carcinoma of the ampulla of Vater is extremely rare and different from the common ampullary adenocarcinoma. The ampullary adenoma is also a rare neoplasm and has the potential to develop an adenocarcinoma. Their coexistence has been rarely reported in the literature. We herein describe an unusual case of a small cell neuroendocrine carcinoma associated with a villous adenoma in the ampulla of Vater with emphasis on computed tomography (CT) and histopathological findings. We also discuss their clinical, histopathological and radiological features as well as possible histogenesis.

EFFECT OF ERYTHROMYCIN ON GASTRIC DYSMOTILITY AND NEUROENDOCRINE PEPTIDES IN RATS WITH DIABETES MELLITUS

Objective To investigate the effect of erythromycin on the contractive activity of the isolated gastric antrum smooth muscle and somatostatin （SS）, vasoactive intestinal peptide （VIP）, motilin （MTL）, and substance P （SP） in plasma and isolated gastric antrum tissue of diabetes mellitus （DM） rat models. Methods Thirty male Sprague-Dawley rats were divided into three groups： control group （n = 10）, DM group （n = 10）, and erythromycin group （DM models with erythromycin treatment, n = 10）. A single dose of streptozotocin （100 mg/kg, dissolved in 0. I mol/L citric acid buffer, pH4.5） was injected intraperitoneally. After 48 to 72 hours, rats with blood glucose above 16.7 mmol/L and urine glucose level to be （＋＋＋ ） to （＋＋＋＋） over one week were considered successful DM models. The resting tension, mean contractile amplitude and fi＇equency of spontaneous change in isolated longitudinal and circular gastric antrum smooth muscle strips were measured. SS, VIP, MTL, and SP levels in plasma and gastric antrum tissue were measured using radioimmunoassay. Results （1） In the isolated gastric antrum smooth muscle strips, the gastric motility parameters were lower in DM group than those in control group except circular smooth muscle contractile amplitude and longitudinal smooth muscle contractile fi＇equency. The gastric motility parameters were significantly strengthened in erythromycin group, compared with DM group except longitudinal smooth muscle resting tension （P 〈 0.01 ）. （2） Plasma SS, VIP, and MTL concentrations in DM group were higher than those in control （P 〈 0.05）, while the SP level decreased （P 〈 0.05）. In the gastric antrum, SS of DM group was significantly higher than that of control group （P 〈 0.01 ）, while SP and MTL levels were lower than those of control group （P 〈 0.05 and P 〈 0.01, respectively）. However, the level of VIP in gastric antrum tissue did not change among three groups. The plasma level of SS in erythromycin group was higher than that of DM group （P 〈 0.05）. （3） The blood glucose was lower in erythromycin group than DM group （P 〈 0.01 ）. Conclusions Erythromycin has direct effects on contractive activity of gastric smooth muscle in diabetic rats, but there are few effects on neuroendocrine peptides. Gastric-motility disorders in diabetic rats have a correlation with the changes of neuroendocrine peptide levels in plasma and gastric antrum tissue.

In vitro study of neuroendocrine regulation over the testicular development in mud crabs Scylla serrata

The reproductive endocrine activities of neuroendocrine organs and androgenic glands (AG) in male Scylla serrata were investigated with co-incubation technology. In vitro studies show that: (1) the AG in Stage Ⅲ can significantly accelerate the development of seminiferous tubules and spermic matu- ration; (2) the brain, thoracic ganglia and optic ganglia have no direct influence over the testicular devel- opment; (3) the brain and thoracic ganglia can significantly promote the growth of the AG cells and highly significantly boost the ratio of Type B cells, while the optic ganglia have no such effects. It is the first time for in vitro investigations to confirm that the brain and thoracic ganglia can regulate testicular development through AG in male crustaceans.

Importance of gastrin in the pathogenesis and treatment of gastric tumors

In addition to regulating acid secretion, the gastric antral hormone gastrin regulates several important cellular processes in the gastric epithelium including proliferation, apoptosis, migration, invasion, tissue remodelling and angiogenesis. Elevated serum concentrations of this hormone are caused by many conditions, particularly hypochlorhydria (as a result of autoimmune or Helicobacter pylori (H pylori)-induced chronic atrophic gastritis or acid suppressing drugs) and gastrin producing tumors (gastrinomas). There is now accumulating evidence that altered local and plasma concentrations of gastrin may play a role during the development of various gastric tumors. In the absence of H pylori infection, marked hypergastrinemia frequently results in the development of gastric enterochromaffi n cell-like neuroendocrine tumors and surgery to remove the cause of hypergastrinemia may lead to tumor resolution in this condition. In animal models such as transgenic INS-GAS mice, hypergastrinemia has also been shown to act as a cofactor with Helicobacter infection during gastric adenocarcinoma development. However, it is currently unclear as to what extent gastrin also modulates human gastric adenocarcinoma development. Therapeutic approaches targeting hypergastrinemia,such as immunization with G17DT, have been evaluated for the treatment of gastric adenocarcinoma, with some promising results. Although the mild hypergastrinemia associated with proton pump inhibitor drug use has been shown to cause ECL-cell hyperplasia and to increase H pylori-induced gastric atrophy, there is currently no convincing evidence that this class of agents contributes towards the development of gastric neuroendocrine tumors or gastric adenocarcinomas in human subjects.

Biochemically curative surgery for gastrinoma in multiple endocrine neoplasia type 1 patients

AIM： To search for the optimal surgery for gastrinoma and duodenopancreatic neuroendocrine tumors in patients with multiple endocrine neoplasia type 1. METHODS： Sixteen patients with genetically confirmed multiple endocrine neoplasia type 1 （MEN 1） and Zollinger-Ellison syndrome （ZES） underwent resection of both gastrinomas and duodenopancreatic neuroendocrine tumors （NETs） between 1991 and 2009. For localization of gastrinoma, selective arterial secretagogue injection test （SASI test） with secretin or calcium solution was performed as well as somatostatin receptor scintigraphy （SRS） and other imaging methods such as computed tomography （CT） or magnetic resonance imaging （MRI）. The modus of surgery for gastrinoma has been changed over time, searching for the optimal surgery： pancreaticoduodenectomy （PD） was first performed guided by localization with the SAST test, then local resection of duodenal gastrinomas with dissection of regional lymph nodes （LR）, and recently pancreas-preserving total duodenectomy （PPTD） has been performed for multiple duodenal gastrinomas. RESULTS： Among various types of preoperative localizing methods for gastrinoma, the SASI test was the most useful method. Imaging methods such as SRS or CT made it essentially impossible to differentiate functioning gastrinoma among various kinds of NETs. However, recent imaging methods including SRS or CT were useful for detecting both distant metastases and ectopic NETs; therefore they are indispensable for staging of NETs. Biochemical cure of gastrinoma was achieved in 14 of 16 patients （87.5%）; that is, 100% in 3 patients who underwent PD, 100% in 6 patients who underwent LR （although in 2 patients （33.3%） second LR was performed for recurrence of duodenal gastri- noma）, and 71.4% in 7 patients who underwent PPTD. Pancreatic NETs more than 1 cm in diameter were resected either by distal pancreatectomy or enucleations, and no hepatic metastases have developed postoperatively. Pathological study of the resected specimens revealed co-existence of pancreatic gastrinoma with duodenal gastrinoma in 2 of 16 patients （13%）, and G cell hyperplasia and/or microgastrinoma in the duodenal Brunner＇s gland was revealed in all of 7 duodenal specimens after PPTD. CONCLUSION： Aggressive resection surgery based on accurate localization with the SASI test was useful for biochemical cure of gastrinoma in patients with MEN 1.Imamura Metal. Curative resection of gastrinoma in MEN-1

Primary hepatic carcinoid:A case report and literature review

Carcinoids are tumors derived from neuroendocrine cells and often produce functional peptide hormones.Approximately 54.5% arise in the gastrointestinal tract and frequently metastasize to the liver.Primary hepatic carcinoid tumors(PHCT) are extremely rare;only 95 cases have been reported.A 65-year-old man came to our attention due to occasional ultrasound findings in absence of clinical manifestations.His previous medical history,since 2003,included an echotomography of the dishomogeneous parenchymal area but no focal lesions.A computed tomography scan performed in 2005 showed an enhanced pseudonodular-like lesion of about 2 cm.Cholangio-magnetic resonance imaging identified the lesion as a possible cholangiocarcinoma.No positive findings were obtained with positron emission tomography.Histology suggested a secondary localization in the liver caused by a low-grade malignant neuroendocrine tumor.Immunohistochemistry was positive for anti chromogranin antibodies,Ki67 antibodies and synaptophysin.Octreoscan scintigraphy indicated intense activity in the lesion.Endoscopic investigations were performed to exclude the presence of extrahepatic neoplasms.Diagnosis of PHCT was established.The patient underwent left hepatectomy,followed by hormone therapy with sandostatine LAR.Two months after surgery he had a lymph nodal relapse along the celiac trunk and caudate lobe,which was histologically confirmed.The postoperative clinical course was uneventful,with a negative follow-up for hematochemical,clinical and radiological investigations at 18 mo post-surgery.Diagnosis of PHCT is based principally on the histopathological confi rmation of a carcinoid tumor and the exclusion of a non-hepatic primary tumor.Surgical resection is the recommended primary treatment for PHCT.Recurrence rate and survival rate in patients treated with resection were 18% and 74%,respectively.

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.

Liver transplantation for metastatic neuroendocrine tumor: A case report and review of the literature

Neuroendocrine tumors are divided into gastrointestinal carcinoids and pancreatic neuroendocrine tumors. The WHO has updated the classification of these lesions and has abandoned the term ＂carcinoid＂. Both types of tumors are divided into functional and non-functional tumors. They are characterized by slow growth and frequent metastasis to the liver and may be limited to the liver for long periods. The therapeutic approach to hepatic metastases should consider the number and distribution of the liver metastases as well as the severity of symptoms related to hormone production and tumor bulk. Surgery is generally considered as the first line therapy. In patients with unresectable liver metastases, alternative treatments are dependent on the type and the growth rate. Initial treatments consist of long acting somatostatin analogs and/or interferon. Streptozocin-based chemotherapy is usually reserved for symptomatic patients with rapidly advancing disease, but generally the therapy is poorly tolerated and its effects are short-lived. Locoregional therapy directed such as hepatic-artery embolization and chemoembolization, radiofrequency thermal ablation and cryosurgery, is often used instead of systemic therapy, if the disease is limited to the liver. However, liver transplantation should be considered in patients with neuroendocrine metastases to the liver that are not accessible to curative or cytoreductive surgery and if medical or Iocoregional treatment has failed and if there are life threatening hormonal symptoms. We report a case of liver transplantation for metastatic neuroendocrine tumor of unknown primary source and provide a detailed review of the world literature on this controversial topic.