嗜铬粒蛋白A在前列腺癌诊断中的意义

目的　探讨血清嗜铬粒蛋白A(CgA)在前列腺癌 (PCa)诊断中的作用。 　方法　采用ELISA法测定 30例健康志愿者 ,35例前列腺癌患者及 10例良性前列腺增生 (BPH)患者的血清CgA ,分析比较各组CgA的水平。 　结果　PCa患者血清CgA(16 2± 12 .5 )ng/ml,与正常对照组 (6 0 .2± 19.8)ng/ml及BPH组 (81.3± 4 3.0 )ng/ml比较差异有显著性意义 (P <0 .0 5 )。血清CgA水平随癌分期的升高而升高 ,D2 患者血清CgA水平明显高于正常对照组及其他分期PCa组 (P分别 <0 .0 1和 <0 .0 5 )。CgA和前列腺特异抗原 (PSA)联合检测可提高对前列腺癌的诊断价值 ,平行试验敏感度83% ,系列试验特异度 93%。　结论　血清CgA水平可应用于前列腺癌的诊断、监测和疗效观察 ,尤其对PSA阴性或伴有远隔转移的病例具有重要意义。     

Serum chromogranin A concentration and intradialytic hypotension in chronic haemodialysis patients

Aim The aim of this study was to investigate the influence of haemodialysis on plasma chromogranin A (CgA) concentration and to assess the relationship between CgA, blood pressure, occurrence of intradialytic hypotension episodes and residual renal function, respectively. Methods The study included 38 chronic haemodialysis patients (24 M, 14 F; mean age 56.2 ± 13.6 years). Plasma CgA and blood pressure were measured before and after a mid-week dialysis. Control group included 10 age- and sex-matched healthy subjects. Results Plasma CgA levels were on average 50-fold higher in HD patients than in the controls (699 ± 138 vs. 14 ± 6 U/L). In HD patients plasma CgA corrected for ultrafiltration rates significantly increased (to 836 ± 214 U/L, P < 0.001) at the end of dialysis procedure. In patients with (n = 8) and without frequent symptomatic intradialytic hypotension episodes predialysis values of CgA were similar (701 ± 169 vs. 698 ± 132 U/L) but post-dialysis were significantly lower in the former group (746 ± 312 vs. 860 ± 177 U/L; P = 0.03) despite a similar rate of ultrafiltration (2675 ± 1009 and 2583 ± 1311 ml, respectively). Accordingly, in patients with intradialytic hypotension an increase of plasma CgA during dialysis was also much lower than in patients without hypotension (45 ± 81 vs. 163 ± 144 U/L; P = 0.001). Conclusions CgA undergoes marked accumulation in renal failure. The increase of plasma CgA during dialysis is impaired in subjects with intradialytic hypotension episodes, which confirms the role of autonomic dysfunction in the pathogenesis of this complication.     

The surgical treatment of gastrinoma in MEN I syndrome patients

The pancreatic component of the multiple endocrine neoplasia type I (MEN I) syndrome is a difficult and controversial problem because the entire endocrine pancreas is diffusely involved with varying degrees of islet-cell hyperplasia, microadenomatosis, and nesidioblastosis. In addition, in patients with functional syndromes, islet-cell tumors usually develop, and these may or may not be malignant. Because of the presumed inability to alleviate or cure the Zollinger-Ellison syndrome (ZES) in MEN patients, total gastrectomy was the treatment of choice before the introduction of H2 antagonists and omeprazole. At present, many physicians and surgeons consider H2 antagonists the best treatment and advise pancreatic exploration only when a gross pancreatic tumor is demonstrated on imaging studies. During the past 10 years we have studied all MEN I patients with ZES without hepatic metastases or gross pancreatic tumors using percutaneous transhepatic selective venous gastrin samplings. Two patterns of gastrin secretion were identified: (1) diffuse from multiple pancreatic sites and (2) localized regional secretion. Four patients from the latter group were selected for attempted surgical "cure" without gastrectomy or total pancreatectomy. Two additional patients are included who had resection of gastrinomas and have maintained basal serum gastrin levels within the normal range for extended periods. The follow-up on these patients ranges from 5 months to 12 years. All six patients have normal basal gastrin values, and those with remaining stomachs require no drug therapy.     

嗜铬粒蛋白A和突触素的动态变化对胰腺神经内分泌肿瘤患者术后的效果评价

目的 研究胰腺神经内分泌肿瘤患者行腹腔镜手术治疗后的嗜铬粒蛋白A和突触素的动态变化,为患者的确诊及预后情况进行监控.方法 选取2013年3月-2015年3月榆林市第一医院收治的45例胰腺神经内分泌肿瘤患者为对象,所有患者均给予腹腔镜手术治疗,观察手术效果并监测患者术后嗜铬粒蛋白A和突触素的水平.组间比较采用x2检验.所有患者均通过电话随访,随访日期截至2017年1月.结果 TNM分期良性患者与恶性患者在术后嗜铬粒蛋白A的检查中发现其阳性表达率分别为85.0％与53.0％,两组比较差异有统计学意义(P＜0.01).而对应突触素的检查中发现其阳性表达率分别为88.0％与89.0％,两组比较差异无统计学意义(P＞0.05);发生淋巴结转移患者和未发生淋巴结转移患者的嗜铬粒蛋白A阳性表达率分别为47.0％与80.0％,两组比较差异有统计学意义(P＜0.01),对应突触素的检查发现阳性表达率分别为87.0％与87.0％,两组比较差异无统计学意义(P＞0.05).结论 腔镜手术治疗胰腺神经内分泌肿瘤是一种微创、安全的手术方式,患者远期生存率高,采用嗜铬粒蛋白A和突触素对患者的术后水平进行监测,能有效评估疾病的发展与预后,而突触素对患者的预后无任何评估意义.     

A case of pancreatitis associated with gastrinoma

A case is presented of a 56 year old man with a history of idiopathic pancreatitis and multiple admissions for Klebsiella sepsis from an intra-abdominal focus, who in February 1980, developed spontaneous jejunal perforations on two occasions due to multiple ulcers in the small intestine associated with multiple hepatic metastases from a gastrin-secreting islet-cell tumor (gastrinoma) of the pancreas. On searching the literature, no other record could be found of an association between pancreatitis and a gastrinoma, although in this patient the two disease processes appear to be inextricably related.     

Long-term cimetidine and anticholinergic therapy in patients with gastrinoma.

Two patients with gastrinomas were treated with cimetidine and an anticholinergic drug for greater than 20 months after exploratory laparotomy disclosed no solitary resectable tumor. Both have done well, and thus this therapy is recommended as a safe and effective alternative to total gastrectomy in reliable patients. Additional therapeutic methods are needed to control tumor growth.     

Catecholamine release induces elevation in plasma lactate levels in patients undergoing adrenalectomy for pheochromocytoma

Study ObjectiveTo determine the relationship between preoperative catecholamine levels and intraoperative peak plasma lactate levels in patients who underwent adrenalectomy for pheochromocytoma.DesignRetrospective observational study.SettingOperating room in one university hospital.MeasurementsThe records of 27 ASA physical status 1 and 2 patients who underwent adrenalectomy for pheochromocytoma were studied. Preoperative catecholamine levels and intraoperative plasma lactate levels were recorded.Main ResultsTwenty cases had high lactate levels (> 2 mmol/L). Preoperative urine epinephrine levels and urine metanephrine levels showed a moderate correlation with intraoperative peak plasma lactate levels (r_s = 0.475 and r_s = 0.499, respectively; Spearman’s rank correlation test). Receiver operating characteristic (ROC) curve analysis for preoperative urine epinephrine levels showed good performance for prediction of high lactate levels [> 2 mmol/L, area under the curve (AUC) = 0.800], whereas ROC for preoperative urine norepinephrine levels showed no predictive performance for high lactate levels.ConclusionsCatecholamine release caused by surgical manipulation may be a possible cause of intraoperative transient lactic acidosis, and it should be considered as a differential diagnosis of intraoperative lactic acidosis. Intraoperative peak plasma lactate level was correlated with preoperative epinephrine-releasing activity.     

Implications of circulating chromogranin A in prostate cancer

OBJECTIVE: To evaluate whether measurement of circulating chromogranin A (CgA) levels provides clinicopathological and prognostic information in prostate cancer. MATERIAL AND METHODS: Plasma CgA levels were measured in 57 patients with histologically confirmed prostate cancer (stage B or less, n=22; stage C, n=10; stage D1, n=2; hormone-naive D2, n=12; hormone-refractory D2, n=11) and in 22 with undetected prostate cancer using an enzyme-linked immunoabsorbent assay. RESULTS: Median plasma CgA levels were significantly higher in patients with prostate cancer than in those with undetected cancer (p=0.0271). Higher stage (p<0.0001) and higher grade (p=0.0412) tumours were also significantly associated with higher plasma CgA levels. Above-normal CgA levels were also detected in 4/27 patients (15%) who underwent radical prostatectomy. Postoperative clinical failure was not reported in the prostatectomy patients; however, prostate-specific antigen (PSA) failure was reported in 44% of patients after a median follow-up period of 20.3 months. Multivariate analysis revealed that the pathological stage of the tumour was the only independent predictive variable for postoperative PSA failure (p=0.0494). Preoperative plasma CgA levels had no impact on postoperative PSA failure in the subgroup (prostatectomy patients). Elevated plasma CgA levels were associated with a poor survival prognosis in patients with stage D2 prostate cancer after a median follow-up period of 22.5 months (p=0.0416). CONCLUSIONS: It was demonstrated in this study that plasma CgA levels in prostate cancer increase with the severity of the disease, especially for progressive hormone-refractory prostate cancer (HRPC), after hormone therapy. Although this cross-sectional study involved only a small number of patients, we believe that plasma CgA levels may effectively predict HRPC status and prognosis in metastatic cases.     

Aggressive resection of metastatic disease in selected patients with malignant gastrinoma.

Fifteen patients with Zollinger-Ellison syndrome followed at the National Institutes of Health with extensive metastatic disease had an actuarial 5-year survival of 20%. Therefore, in 1982 a prospective study to examine the effect and feasibility of removing all gross tumor in selected patients with extensive metastatic disease was instituted. Five patients with extensive metastatic gastrinoma confined to the abdomen in whom imaging studies suggested the possibility of complete surgical resection were entered into this study and underwent attempted complete surgical resection and chemotherapy with streptozotocin, doxorubicin, and 5-fluorouracil. Median follow-up was 24 months. Surgical resection of all gastrinoma was possible in 4/5 patients attempted. In one patient in whom all gross disease could not be resected, the residual tumor progressed and the patient died 19 months after operation. All four patients with all disease resected appeared to benefit since all of them had a significant reduction in antisecretory medications and are enjoying normal activity and work. Three patients have had no detectable tumor on follow-up, and two of these patients are clinically and biochemically "cured" with normal fasting gastrin levels and negative provocative gastrin tests at 14 and 32 months. Therefore, aggressive resection of metastatic disease in selected patients with malignant gastrinoma is recommended.     

Current approach to the management of tumoral process in patients with gastrinoma

One hundred forty-four consecutive patients with Zollinger-Ellison syndrome (ZES) were reviewed at Bichat Hospital in 1985. The population included 117 patients with a demonstrated tumoral process, 10 with islet-cell hyperplasia, and 17 in whom no anatomical findings had yet been demonstrated. Patients in the 2 latter categories had clinical and biological features of ZES. Thirty-five patients had multiple endocrine neoplasia type I (MEN I). Hyperparathyroidism was the most frequently associated endocrine disorder and required neck surgery in 65% of the patients. Pancreatic surgery failed in 61% of these individuals. Preoperative imaging techniques allowed a correct topographic diagnosis in only 1 out of every 2 patients. In 27 patients with negative preoperative imagery, pathological findings were revealed at surgery.Since 1974, major gastric antisecretory agents were used systematically in practically every patient which recommended either no surgical intervention (18 patients) or in most cases elective abdominal surgery. H₂-blockers have, in this series, clearly induced a reduction of the classical surgery combining total gastrectomy with gastrinoma removal and fostered gastrinoma surgery alone. The best chance of getting an apparently complete cure is offered to patients with ectopic gastrinomas, particularly those with duodenal wall tumors, and to a lesser degree, removable pancreatic tumors. Malignancy is frequent: 36 patients had hepatic metastases, which adversely and considerably influenced the probability of survival in ZES patients. Chemotherapy was used in 14 individuals with encouraging results.

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Resumen Ciento cuarenta y cuatro pacientes consecutivos con síndrome de Zollinger-Ellison (SZE) fueron revisados en el Hospital Bichat en 1985. La población incluyó 117 pacientes con proceso tumoral demostrado, 10 con hiperplasia de células insulares y 17 en quienes no se logró demostrar hallazgo anatómico alguno. Los pacientes en las 2 últimas categorías presentaron características clínicas y biológicas de SZE. En 35 pacientes con síndrome de neoplasia endocrina múltiple tipo I, el hiperparatiroidismo apareció como la alteración endocrina asociada más frecuente y requirió cirugía cervical en 65% de los casos. La cirugía pancreática falló en el 61% de estos individuos. Técnicas de imagenología preoperatoria lograron el diagnóstico topográfico correcto en sólo 1 de cada 2 pacientes. En 27 pacientes con imágenes diagnósticas preoperatorias negativas los hallazgos patológicos sólo vinieron a ser evidentes después de la cirugía.A partir de 1974 se han utilizado en forma sistemática los principales agentes antisecretorios en prácticamente todo paciente no sometido a cirugía (18 casos) o bien en la mayoría de los casos sometidos a cirugía abdominal. En esta serie los bloqueadores H₂ han logrado una clara reducción de la cirugía clásica que combina la gastrectomía total con la resección del gastrinoma en favor de la cirugía para gastrinoma solamente. La mejor oportunidad de lograr una curación aparentemente completa se presenta en los casos de gastrinomas ectópicos, en especial los tumores de la pared duodenal, y en menor grado en el caso de tumores pancreáticos resecables.La malignidad es frecuente: se presentaron 36 casos con metástasis hepáticas, y este hallazgo mostró una influencia adversa considerable sobre la posibilidad de supervivencia en los pacientes con SZE. La quimioterapia fue utilizada en 14 casos con resultados promisorios.

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Résumé Une série de 144 sujets présentant un syndrome de Zollinger-Ellison (ZES) a été étudiée en 1985 à l'hôpital Bichat. Elle comportait 117 cas de tumeur individualisée, 10 cas d'hyperplasie insulaire et 17 cas sans lésion apparente. Les sujets des 2 derniers groupes présentaient des signes cliniques et biologiques de ZES. Trente-cinq présentaient un MEN I, l'hyperparathyroïdisme étant l'affection endocrinienne associée la plus fréquente et nécessitant l'intervention dans 65% des cas. La chirurgie pancréatique fut inefficace chez 61% d'entre eux. Les techniques d'imagerie préopératoire permirent de porter le diagnostic topographique exact de la lésion une fois sur deux seulement. Chez 27 sujets dont les investigations étaient restées négatives, l'exploration chirurgicale permit de découvrir la lésion.Depuis 1974 les agents antisécréteurs gastriques ont été employés systématiquement chez tout malade, ce qui permit ou d'éviter l'intervention chirurgicale (18 cas) ou l'intervention abdominale élective dans la majorité des cas. Dans cette série les anti-H₂ ont entraîné une réduction très nette du traitement chirurgical classique (associant la gastrectomie totale à l'exérèse du gastrinome) et ont favorisé l'éradication isolée du gastrinome. Les meilleurs chances de guérison concernent les tumeurs de siège ectopique, dans la paroi duodénale en particulier, et à un moindre degré les tumeurs extirpables du pancréas.

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Presented at the International Association of Endocrine Surgeons in Paris, September 1985.     

Utility of FDG-PET for investigating unexplained plasma CEA elevation in patients with colorectal cancer.

OBJECTIVE: To assess the potential role of positron emission tomography (PET) with 2-[18F]fluoro-2-deoxy-D-glucose (FDG) in patients with unexplained rising carcinoembryonic antigen (CEA) levels after the treatment of colorectal cancer. BACKGROUND: A rising CEA level after the resection of colorectal cancer is an early indicator of tumor recurrence. However, conventional imaging techniques have limited sensitivity for detecting recurrent disease in such patients. Especially after surgical intervention, FDG-PET is rapidly gaining an important role in establishing the extent of disease in the oncology patient. METHODS: Twenty-two patients with abnormal CEA levels and normal results of conventional methods of tumor detection were studied with FDG-PET. The PET results were compared with pathologic findings (n = 9) and long-term radiologic and clinical follow-up (n = 13). RESULTS: FDG-PET was abnormal in 17 of 22 patients. Tissue sampling was available in 7 of these 17 patients; all of these had recurrent disease. Definitive curative surgical intervention was performed in four patients. Subsequent dedicated imaging findings and clinical course confirmed the presence of extensive disease in 8 of the remaining 10 patients; the PET results in the other 2 patients were considered falsely positive. FDG-PET was negative in 5 of 22 patients. No disease was found by tissue sampling (n = 2) and clinical follow-up (n = 3). Overall, the positive-predictive value for PET was 89%, (15 of 17) and the negative-predictive value was 100% (5 of 5). CONCLUSIONS: When conventional examinations are normal, FDG-PET is a valuable imaging tool in patients who have a rising CEA level after colorectal surgery.     

Management and outcome of patients with sporadic gastrinoma arising in the duodenum

BACKGROUND: Primary duodenal gastrinomas are now recognized as a common etiology for patients with sporadic Zollinger Ellison Syndrome (ZES); however, the clinical and pathologic features of this condition and long-term outcome after operation are not well characterized. METHODS: Between November 1982 and September 2000, 63 patients diagnosed with sporadic ZES underwent resection of a primary duodenal gastrinoma and regional nodal metastases with curative intent. Data from a prospectively maintained database were reviewed for clinical and pathologic parameters relating to primary tumor size, location, frequency of lymph node metastases, and disease-specific and disease-free survival. RESULTS: There were 41 males and 22 females (mean age, 48.6 years). The majority of duodenal gastrinomas were in the first or second portions of the duodenum (83%). Tumor size ranged from 0.2 to 2.0 cm with 62% measuring less than 1.0 cm. Sixty percent of individuals had regional lymph node metastases identified primarily in proximity to the primary tumor. At a median 10-year follow-up, the overall disease-specific and disease-free survivals were 100% and 60%, respectively. Actuarial 10-year disease-free survival was significantly higher for patients without lymph node metastases versus those with lymph node metastases (78% versus 48%, P = 0.0137). CONCLUSIONS: Duodenal gastrinomas in patients with sporadic ZES are frequently small, most commonly located in the proximal duodenum, and associated with regional lymph node metastases in 60%. Disease-free survival is lower for patients with regional lymph node metastases suggesting that a more systematic lymphadenectomy to extirpate occult disease may be indicated in this group.     

Surgical management of gastrinoma

In eight of 10 patients with Zollinger-Ellison syndrome resection of all visible tumor tissue was combined with gastrectomy. The results in this group of patients, as in other series reported in the literature, suggest that excision of gastrinoma by partial pancreatectomy or enucleation can be combined safely with gastrectomy. Perhaps excision of tumor is preferable in the management of patients with solitary tumor who do not have the multiple endocrine neoplasia syndrome. We await further follow-up studies and experience with additional patients before judging this thesis of tumor resection with gastric preservation.     

Prospective study of gastrinoma localization and resection in patients with Zollinger-Ellison syndrome.

In 1982, a prospective study was initiated of 52 consecutive patients with proven Zollinger-Ellison syndrome (ZES), involving surgical exploration with the goal of removing the gastrinoma after an extensive protocol to localize the tumor. Each patient underwent ultrasound, computed tomography (CT) with oral/intravenous (IV) contrast, and selective arteriography. Eighteen patients had metastatic disease identified by imaging studies and confirmed by percutaneous biopsies, and two patients had multiple endocrine neoplasia type I (MEN-I) with negative imaging studies; therefore, these 20 patients did not undergo laparotomy. Each of the remaining 32 patients (3 with MEN-I and positive imaging studies) underwent laparotomy, and gastrinomas were removed in 20 patients. Preoperative ultrasound localized tumors in 20% of patients, CT in 40%, arteriography in 60%, and any of the modalities in 70% of patients. Infusion CT and arteriography were 100% specific. In 18 patients with either negative imaging (17) or false-positive imaging (1 ultrasound), gastrinomas were found and removed in six patients (33%). Twenty-four gastrinomas were found in 20 patients at laparotomy: eight in lymph nodes around the pancreatic head, four in the pancreatic head, one in the pancreatic body, three in the pancreatic tail, three in the pyloric channel, one in the duodenal wall, two in the jejunum at the ligament of Treitz, one in the ovary, and multiple liver metastases in one patient. If one excludes patients with MEN-I or liver metastatic disease, 12/28 (43%) of patients were biochemically "cured" immediately after operation. This result decreased to 7/23 (30%) with greater than 6 months follow-up. No patients with gastrinomas resected have developed recurrent gastrinoma on follow-up imaging studies (longest follow-up: 4 years). This study indicates that 95% of metastatic gastrinoma can be diagnosed before operation and that, by a combination of careful imaging studies and thorough exploration at surgery, 30% of patients with gastrinomas may be curable.