Current surgical management of pancreatic endocrine tumor liver metastases

BACKGROUND: The management of metastatic disease in pancreatic endocrine tumors (PETs) demands a multidisciplinary approach and the cooperation of several medical specialties. The role of surgery is critical, even when a radical excision cannot always be achieved. DATA SOURCES: A PubMed search of relevant articles published up to February 2011 was performed to identify current information about PET liver metastases regarding diagnosis and management, with an emphasis on surgery. RESULTS: The early diagnosis of metastases and their accurate localization, most commonly in the liver, is very important. Surgical options include radical excision, and palliative excision to relieve symptoms in case of failure of medical treatment. The goal of the radical excision is to remove the primary tumor bulk and all liver metastases at the same time, but unfortunately it is not feasible in most cases. Palliative excisions include aggressive tumor debulking surgeries in well-differentiated carcinomas, trying to remove at least 90% of the tumor mass, combined with other additional destructive techniques such as hepatic artery embolization or chemoembolization to treat metastases or chemoembolization to relieve symptoms in cases of rapidly growing tumors. The combination of chemoembolization and systemic chemotherapy results in better response and survival rates. Other local destructive techniques include ethanol injection, cryotherapy and radiofrequency ablation. CONCLUSION: It seems that the current management of PETs can achieve important improvements, even in advanced cases.

Pathological differential diagnosis of solid-pseudopapillary neoplasm and endocrine tumors of the pancreas

AIM:To investigate differential points of solid-pseudo-papillary neoplasm (SPN) of the pancreas and pancre-atic endocrine tumor (PET).METHODS:Ten cases of SPN and fourteen cases of PET were studied in this retrospective study. Clinical and pathologic features,immunostaining reactions and β-catenin gene mutations were analyzed.RESULTS:The mean age of SPN patients was 25.6 years and these patients had no specific symptoms. The mean diameter of the tumors was 11.0 cm,9/10 cases were cystic or a mixture of solid and cystic structures,and there was hemorrhage and necrosis on the cut surface in 8/10 (80%) cases. Characteristic pseudo-papillary structure and discohesive appearance of the neoplastic cells were observed in all 10 (100%) cases. The results of immunostaining showed that nuclear expression of β-catenin and loss of E-cadherin in all the cases,was only seen in SPN. Molecular studies discov-ered that 9/10 (90%) cases harbored a point mutation of exon 3 in β-catenin gene. On the other hand,the mean age of PET patients was 43.1 years. Eight of 14 cases presented with symptoms caused by hypoglyce-mia,and the other 6 cases presented with symptoms similar to those of SPN. The mean size of the tumors was 2.9 cm,most of the tumors were solid,only 3/14 (21%) were a mixture of solid and cystic structures,and macroscopic hemorrhage and necrosis were much less common (3/14,21%). Histologically,tumor cells were arranged in trabecular,acinar or solid patterns and demonstrated no pseudopapillary structure and discohesive appearance in all 14 (100%) cases. The results of immunostaining and mutation detection were completely different with SPN that membrane and cytoplastic expression of β-catenin without loss of E-cadherin,as well as no mutation in β-catenin gene in all the cases. CONCLUSION:Both macroscopic and microscopic features of SPN are quite characteristic. It is not difficult to distinguish it from PET. If necessary,immunos-taining of β-catenin and E-cadherin is quite helpful to make the differential diagnosis.

Microwave ablation combined with hepatectomy for treatment of neuroendocrine tumor liver metastases

BACKGROUND Hepatectomy is the first choice for treating neuroendocrine tumor liver metastases.However,most patients with neuroendocrine tumor liver metastases are not suitable for hepatectomy.Ablation combined with hepatectomy can be an alternative to liver resection.AIM To explore the clinical effect of microwave ablation combined with hepatectomy for the treatment of neuroendocrine tumor liver metastases.METHODS In this study,the data of patients who underwent microwave ablation combined with hepatectomy for the treatment of neuroendocrine tumor liver metastases from June 2015 to January 2018 were reviewed.Before the operation,the patients did not receive any treatment for liver neuroendocrine tumors.After a multidisciplinary expert group discussion,all patients were deemed unsuitable for liver resection.All patients were diagnosed with neuroendocrine tumors by pathology.The overall survival time and progression-free survival time were followed by telephone calls and outpatient visits after surgery.RESULTS Eleven patients with neuroendocrine tumor liver metastases were treated by microwave ablation combined with hepatectomy between June 2015 and January 2018.The median number of liver metastatic nodules was 4(range,2 to 43).The median number of lesions resected was 1(range,1 to 18),and the median number of lesions ablated was 3(range,1 to 38).The mean operation time was 405.6(±39.4)min.The median intraoperative blood loss was 600 mL(range,50 to 3000).Ten patients had a fever after surgery.The median duration of fever was 3 d(range,0 to 21).Elevated bilirubin levels occurred in all patients after surgery.The median bilirubin on the first day after surgery was 28.5(range,10.7 to 98.9)μmol/L.One patient developed respiratory failure,renal insufficiency,and pneumonia after the operation.No patient died postoperatively during hospitalization.The mean overall survival time after surgery was 34.1(±3.7)mo,and the median progression-free survival time was 8(range,2 to 51)mo.One year after surgery,ten patients survived and five patients survived without progression.Three year after surgery,eight patients survived and two patients survived without progression.CONCLUSION Microwave ablation combined with hepatectomy not only makes the patients obtain a survival rate similar to that of patients undergoing hepatectomy,but also has a low incidence of postoperative complications.

Autoimmune pancreatitis with atypical imaging findings that mimicked an endocrine tumor

Autoimmune pancreatitis(AIP) is a rare cause of recurrent acute pancreatitis or chronic pancreatitis in middleaged patients,and is characterised by a marked infiltration of lymphocytes and plasma cells in pancreatic tissue.Diagnosis of focal forms can be diff icult as AIP may mimic pancreatic adenocarcinoma.Pediatric cases of AIP are exceptional.We report the case of a 15-yearold girl who had a focal AIP and associated cholangitis,with a very unusual vascularized mass that mimicked a pancreatic endocrine tumor.The diagnosis was obtained by a pancreatic biopsy,thus avoiding surgical resection,and all the clinical,biological and radiological abnormalities resolved after steroid therapy with 6 mo of follow-up.

Clinical analysis of malignant pancreatic endocrine tumors:reports of 27 cases

To investigate clinicopathological features,diagnosis and treatment of malignant pancreatic tumors.Methods A retrospective clinical analysis was made in 27 cases of malignant pancreatic tumors admitted from 1989 to 2003.Results Tumors were surgically resected in 22 patients.Tumor infiltration into surrounding organs was found in 13 cases.Four patients had lymph nodes metastasis and 5 had liver metastasis.Two cases were found tumor embolus in vascular or lymph tube.Neural invasion was found in 3.Conclusion Malignant pancreatic tumors has good prognosis.Aggressive attempts of surgical management should be performed.6 refs,1 tab.

Diagnosis and surgical treatment of pancreatic endocrine tumors in 36 patients:a single-center report

Background Pancreatic endocrine tumors （PETs） are rare and their surgical treatment is often debated. The purpose of this retrospective study was to analyze the diagnosis and surgical strategy of functioning and non-functioning PETs. Methods From May 1980 to March 2006, 36 patients with pancreatic endocrine tumors at the Second Affiliated Hospital of Zhejiang University were retrospectively studied. Results Among the 36 patients, 29 （81%） had functioning tumors, and 7 （19%） had nonfunctioning tumors. Ninety-two percent of insulinomas were benign, whereas 4 （57%） of nonfunctioning PETs were malignant. The size of functioning tumors was （2.3i-0.3） cm, that of nonfunctioning tumors was less than （5.1^-0.5） cm. The combination CT and transabdominal ultrasonography resulted in a diagnostic sensitivity of 84%. Thirty-three primary lesions were precisely located in 32 patients （89%）. Atypical tumor resection was performed for 73% of functioning tumors, while typical pancreatectomy was performed for 6 （85%） of nonfunctioning tumors. Moreover, 5 liver resections and 1 lymph node dissection were performed. During the follow-up, fifteen complications occurred in 12 （36%） patients after operation. The 5-year survival rate for patients with benign tumors was 92% compared to 50% for those with malignant tumors. Surgical cure was achieved in 95% of patients with benign insulinomas. Conclusions Surgical strategy for PETs depends on the size and location of the tumor and the risk of malignancy. The optimal surgical procedure is key to prevent postoperative complication. Radical resection including initial and metastatic lesion may benefit patients with maliqnant PETs.

SIGNIFICANCE OF EXPRESS OF SOME NONHORMONAL ANTIGENS IN PANCREATIC ENDOCRINE TUMORS

Objective: To study the express of some nonhormonal antigens in pancreatic endocrine tumors. Methods: The nonhormonal antigens including Alpha subunit of human chorionic gonadotropin (α HCG), progesterone receptors (PR), 7B2, HISL 19, in normal pancreatic islets and in 52 cases of pancreatic endocrine tumors (PET) were investigated by immunohistochemistry. Results: It was found that HCG can be detected in PET but not in normal islet cells. HCG immunoreactivity was expressed by 3 of 28 (10.7%) benign PET and by 14 of 24 (58.3%) malignant PET.PR was found by 20 of 28(71.4%) benign PET and by 7 of 24 (29%) malignant PET. 7B2 was detected by 23 of 28 (82.1%) benign PET and by 13 of 24 (54.2%) malignant PET. HISL 19 was appeared by 23 of 28 benign PET and by 11 of 24 (46%) malignant PET. Golgitype persisted in 87.5% malignant tumors. Conclusion: The assay of nonhormonal antigens may be well defined the clinico pathological characteristics of PET.

STUDY ON EXPRESS OF a-HCG AND a-HCGmRNA IN PANCREATIC ENDOCRINE TUMORS

The antigen Alpha subunit of human chorionic gonadotropin (α HCG) and a HCGmRNA in pancreatic endocrine tumors (PET) were investigated by immuno histochemistry and in situ hybridization. It was found that α HCG can be detected in PET buy not in normal islet cells. α HCG immunoreactivity was expressed by 5 of 28 (18%) in benign PET and 14 of 24 (58.3%) in malignant PET. Using in situ hybridization of α HCGmRNA, a strong signal in PET was obtained. The clinico pathological significance of α HCG in PET was discussed.

Mixed epithelial endocrine neoplasms of the colon and rectum–An evolution over time:A systematic review

BACKGROUND Mixed tumors of the colon and rectum,composed of a combination of epithelial and endocrine elements of benign and malignant potential are rare neoplasms.These can occur anywhere in the gastrointestinal tract and are often diagnosed incidentally.Though they have been a well-documented entity in the pancreas,where the exocrine-endocrine mixed tumors have been known for a while,recognition and accurate diagnosis of these tumors in the colon and rectum,to date,remains a challenge.This is further compounded by the different terminologies that have been attributed to these lesions over the years adding to increased confusion and misclassification.Therefore,dedicated literature reviews of these lesions in the colon and rectum are inconsistent and are predominantly limited to case reports and case series of limited case numbers.Though,most of these tumors are high grade and of advanced stage,intermediate and low grade lesions of these mixed tumors are also increasingly been reported.There are no established independent consensus based guidelines for the therapeutic patient management of these unique lesions.AIM To provide a comprehensive targeted literature review of these complex mixed tumors in the colon and rectum that chronicles the evolution over time with summarization of historical perspectives of terminology and to further our understanding regarding their pathogenesis including genomic landscape,clinicoradiological features,pathology,treatment,prognosis,the current status of the management of the primary lesions,their recurrences and metastases.METHODS A comprehensive review of the published English literature was conducted using the search engines PubMed,MEDLINE and GOOGLE scholar.The following search terms[“mixed tumors colon”OR mixed endocrine/neuroendocrine tumor/neoplasm/lesion colon OR adenocarcinoma and endocrine/neuroendocrine tumor colon OR mixed adenocarcinoma and endocrine/neuroendocrine carcinoma colon OR Amphicrine tumors OR Collision tumors]were used.Eligibility criteria were defined and all potential relevant items,including full articles and/or abstracts were independently reviewed,assessed and agreed upon items were selected for in-depth analysis.RESULTS In total 237 full articles/abstracts documents were considered for eligibility of which 45 articles were illegible resulting in a total of 192 articles that were assessed for eligibility of which 139 have been selected for reference in this current review.This seminal manuscript is a one stop article that provides a detailed outlook on the evolution over time with summarization of historical perspectives,nomenclature,clinicoradiological features,pathology,treatment,prognosis and the current status of the management of both the primary lesions,their recurrences and metastases.Gaps in knowledge have also been identified and discussed.An important outcome of this manuscript is the justified proposal for a new,simple,clinically relevant,non-ambiguous terminology for these lesions to be referred to as mixed epithelial endocrine neoplasms(MEENs).CONCLUSION MEEN of the colon and rectum are poorly understood rare entities that encompass an extensive range of heterogeneous tumors with a wide variety of combinations leading to tumors of high,intermediate or low grade malignant potential.This proposed new revised terminology of MEEN will solve the biggest hurdle of confusion and misclassification that plagues these rare unique colorectal neoplasms thus facilitating the future design of multi institutional prospective randomized controlled clinical trials to develop and evaluate newer therapeutic strategies that are recommended for continued improved understanding and personal optimization of clinical management of these unique colorectal neoplasms.

Malignant carcinoid tumor of the cystic duct:a rare cause of bile duct obstruction

BACKGROUND:Carcinoid tumors of the extrahepatic biliary tree are extremely rare malignancies,accounting for 0.2%-2%of all gastrointestinal carcinoid tumors,while carcinoids of the cystic duct are an uncommon entity and an extremely unusual cause of bile duct obstruction.METHODS:After an extensive literature review,we retrospectively analysed 61 cases of carcinoid tumor of the biliary tree as well as one additional case of a 60-yearold female with symptoms and laboratory/imaging examination findings compatible with those of a malignant biliary tract obstruction.At laparotomy,resection of the gallbladder and common bile duct was performed.Histological study revealed a well-differentiated neuroendocrine carcinoma of the cystic duct.The patient remained disease-free at 16 months.RESULTS:Our presentation is the seventh case reported in the world literature.Compared to cholangiocarcinoma,analysis of the reviewed group indicates an increased incidence of extrahepatic carcinoid tumors in younger persons along with a slight female predominance.Statistically,the most common anatomic location is the common bile duct,followed by the perihilar region and the cystic duct.Jaundice is the most common finding.Curative surgery was realized in the majority of cases and longterm disease-free survival was achieved when surgery was curative.CONCLUSIONS:Carcinoid tumors obstructing the biliary tree are extremely difficult to diagnose preoperatively,and nearly impossible to differentiate from non-neuroendocrine tumors.As surgery offers the only potential cure for both biliary carcinoids and cholangiocarcinoma,we recommend aggressive surgical therapy as the treatment of choice in every case of potentially resectable biliary tumor.

The expression of p27^(Kip1) and β-catenin in multiple endocrine neoplasia type 1-related parathyroid tumors

Objective To explore tissue expression of cyclin-dependent kinase inhibitor p27Kip1 andβ-catenin in multiple endocrine neoplasia type1（MEN1）-related parathyroid tumors（MHPT）.Methods Immunohistochemistry was performed to analyze the expression of p27Kip1 andβ-catenin in parathyroid glands from 31 subjects

Epidemiological study of a von Hippel-Lindau family in northwest China

von Hippel-Lindau(VHL)disease is a rare,inherited neoplastic disease characterized by hemangioblastomas(HBL)of the central nervous system(CNS),retinal angiomas,renal cell carcinomas(RCC),pancreatic endocrine tumors(PETs),pheochromocytomas,paragangliomas,and visceral cysts.We encountered a large VHL family in northwest China and conducted a systematic screening of the family members based on their epidemiological and clinical characteristics.A self-designed questionnaire was used to collect the general sociodemographic and health information of the family members.For the preliminary family screening,physical examination and abdomen B ultrasonography were performed.The suspected patients were subjected to cranial computerized tomography and fundus examination.The clinical data of the patients with confirmed VHL disease were collected from hospital records.A total of 63 lineal descendants in six generations were observed in the family(generations O,A,B,C,D,E),including 9 dead suspected cases(6 males,3 females)and 10 living cases(2 males,8 females).Among the 10 living cases,4,2,1,3,4,8,and 2 manifested HBLs of the CNS,PETs,RCC,pancreatic cysts,renal cysts,pheochromocytomas(4 hemi and 4 bilateral),and paragangliomas,respectively.Data showed that the morbidity of VHL disease in generation C was lower than that in generation B,but the age of onset was younger.This study is the first to report VHL disease in northwest China and VHL-associated PET cases in Chinese.Therefore,follow-up checkups of the family should be focused on younger generations.Proper family screening protocols should be followed for the treatment of patients with VHL disease.