Gastric carcinoids(GCs),which originate from gastric enterochromaffin-like(ECL) mucosal cells and account for 2.4% of all carcinoids,are found increasingly in the course of upper gastrointestinal tract endoscopy.Curre...Gastric carcinoids(GCs),which originate from gastric enterochromaffin-like(ECL) mucosal cells and account for 2.4% of all carcinoids,are found increasingly in the course of upper gastrointestinal tract endoscopy.Current nosography includes those occurring in chronic conditions with hypergastrinemia,as the type 1 associated with chronic atrophic gastritis,and the type 2 associated with Zollinger-Ellison syndrome in multiple endocrine neoplasia type 1,and type 3,which is unrelated to hypergastrinemia and is frequently malignant,with distant metastases.The optimal clinical approach to GCs remains to be elucidated,depending upon type,size and number of carcinoids.While there is agreement concerning the treatment of type 3 carcinoids,for types 1 and 2,current possibilities include simple surveillance,endoscopic polypectomy,surgical excision,associated or not with surgical antrectomy,or total gastrectomy.Moreover,the recent introduction of somatostatin analogues represents a therapeutic option of possibly outstanding relevance.展开更多
AIM: To assess the results of endoscopic mucosal re-section with a ligation device (EMR-L) combined with three dimensional endoscopic ultrasonography (3D-EUS) using an ultrasonic probe for rectal carcinoids. In additi...AIM: To assess the results of endoscopic mucosal re-section with a ligation device (EMR-L) combined with three dimensional endoscopic ultrasonography (3D-EUS) using an ultrasonic probe for rectal carcinoids. In addition, diagnosis of the depth and size of lesions by EUS was evaluated. METHODS: Between January 2003 and March 2007, 20 patients underwent EMR-L with 3D-EUS using an ultrasonic probe (group A). 3D-EUS was combined with EMR-L at the time of injection of sterile physiological saline into the submucosal layer. For comparison, 14 rectal carcinoids that had been treated by EMR-L with-out 3D-EUS between April 1998 and December 2002 were evaluated as historical controls (group B). EUS was conducted for all of the patients before treatment to evaluate tumor diameter and depth of invasion. The percentage of complete resection and the verti-cal resection margin were compared between the two groups. RESULTS: The depth of invasion upon histopathologi-cal examination was in complete agreement with the pre-operative fi ndings by EUS. The tumor diameter de-termined by EUS approximated that found in the tissue samples. There were no signifi cant differences in the gender, tumor sites or tumor diameters between the two groups. The rate of complete resection for groups A and B was 100% and 71%, respectively (P < 0.05). The vertical resection margin of group A was longer than that of group B. CONCLUSION: EMR-L is effective as an endoscopictreatment for rectal carcinoids. In combination with 3D-EUS, safe and complete resection is further as-sured.展开更多
AIM： To investigate the expression of cyclin-dependent kinase inhibitors p21 and p27 in gastric well differentiated endocrine tumors （GWDET） （ECLocell carcinoids）.METHODS： The expressions of p21 and p27 were exa...AIM： To investigate the expression of cyclin-dependent kinase inhibitors p21 and p27 in gastric well differentiated endocrine tumors （GWDET） （ECLocell carcinoids）.METHODS： The expressions of p21 and p27 were examined immunhistochemically in endoscopic biopsy specimens from 16 patients matching the diagnostic criteria of GWDET. Percentage of positive nuclear staining either weak or strong was noted. The association of immunoexpressions with age, gender, tumor localization, multifocality and accompanying chronic atrophic gastritis, neuroendocrine cell hyperplasia （NEH）, neuroendocrine dysplasia （NED）, intestinal metaplasia （IM）, Ki-67 proliferation index and clinical outcome were also evaluated.RESULTS： All cases expressed p27 with a mean expression score of 43.6%, while 31.3% of the cases showed any p21 expression, p21 and p27 immunoexpressions were significantly correlated with each other （P 〈 0.01）, and the p21-expressing group had higher p27 expression scores （68% vs 22%）. p21 and p27 expressions were lower in women, in non-atrophic mucosa and cases whose tumors were located somewhere other than fundus without submucosal extension. On contrary, p21 and p27 expressions were higher in males and the patients with submucosal extension and atrophic gastritis. Cases presenting lower p27 scores had solitary tumors showing neither NEH-NED nor IM. Despite, cases with lower p21 expression presented multifocal tumors accompanied by NEH-NED. However, no correlation of p21 and p27 expressions was found with age and Ki-67 expression.CONCLUSION： p27 is widely expressed in GWDETs, while p21 expression is sparse and observed in two thirds of the cases. Loss of p21 and p27 expressions may be correlated with different carcinoid tumor subtypes; however,more studies are needed to assess the role of these prospective markers in gastrointestinal endocrine tumors.展开更多
An estimated 25% to 30% of all neuroendocrine tumors (NETs) have their origin in the bronchial tree and into the lungs. Although lung NETs account for less than 1% of all pulmonary malignancies, the incidence of these...An estimated 25% to 30% of all neuroendocrine tumors (NETs) have their origin in the bronchial tree and into the lungs. Although lung NETs account for less than 1% of all pulmonary malignancies, the incidence of these neoplasms has risen precipitously since the mid 1970s. Currently, according to the 2004 World Health Organization categorization, these tumors are separated into 4 subtypes characterized by increasing biologic aggressiveness: low-grade typical carcinoid (TC), intermediate-grade atypical carcinoid (AC), high-grade large-cell neuroendocrine carcinoma (LCNEC) and small-cell carcinoma (SCLC). Surgery is the treatment of choice for typical and atypical carcinoid lung NETs with loco-regional disease. At diagnosis up to 64% of patients with atypical carcinoid lung NETs present with lymph node metastases, and 5-year survival ranges from 61% to 88%. In contrast, lymph node metastases are present in fewer than 15% of typical carcinoid lung NETs, and 5-year survival exceeds 90%. To date, there is no recognized standard of treatment for advanced carcinoid lung NETs. In recent years only two trials reported intriguing results regarding lung NETs: a phase 2 retrospective study of dacarbazine derivative temozolomide and the phase 3, RADIANT-2 trial in advanced NETs. Successful management requires a multidisciplinary team management. This review is restricted to typical/atypical NETs.展开更多
AIM: To assess the therapeutic value of endoscopic mucosal resection (EMR) under micro-probe ultrasound guidance for rectal carcinoids less than 1 cm in diameter. METHODS: Twenty-one patients pathologically diagnosed ...AIM: To assess the therapeutic value of endoscopic mucosal resection (EMR) under micro-probe ultrasound guidance for rectal carcinoids less than 1 cm in diameter. METHODS: Twenty-one patients pathologically diagnosed with rectal carcinoids following colonoscopy in our hospital from January 2007 to November 2012 were included in this study. The patients consisted of 14 men and 7 women, with a mean age of 52.3 ± 12.2 years (range: 36-72 years). The patients with submucosal tumors less than 1 cm in diameter arising from the rectal and muscularis mucosa detected by micro-probe ultrasound were treated with EMR and followed up with conventional endoscopy and micro-probe ultrasound. RESULTS: All of the 21 tumors were confirmed by micro-probe ultrasound as uniform hypoechoic masses originating from the rectal and muscularis mucosa, without invasion of muscularis propria and vessels, and less than 1 cm in diameter. EMR was successfully completed without bleeding, perforation or other complications. The resected specimens were immunohistochemically confirmed to be carcinoids. Patients were followed up for one to two years, and no tumor recurrence was reported. CONCLUSION: EMR is a safe and effective treatment for rectal carcinoids less than 1 cm in diameter.展开更多
Gastric carcinoids(GCs) are classified as: type Ⅰ,related to hypergastrinemia due to chronic atrophic gastritis(CAG), type Ⅱ, associated with Zollinger-Ellison syndrome in multiple endocrine neoplasia type 1, and ty...Gastric carcinoids(GCs) are classified as: type Ⅰ,related to hypergastrinemia due to chronic atrophic gastritis(CAG), type Ⅱ, associated with Zollinger-Ellison syndrome in multiple endocrine neoplasia type 1, and type Ⅲ, which is normogastrinemic. The management of type-Ⅰ gastric carcinoids(GC1s) is still debated,because of their relatively benign course. According to the European Neuroendocrine Tumor Society guidelines endoscopic resection is indicated whenever possible;however, it is not often feasible because of the presence of a multifocal disease, large lesions, submucosal invasion or, rarely, lymph node involvement. Therefore,somatostatin analogs(SSAs) have been proposed as treatment for GC1 s in view of their antisecretive,antiproliferative and antiangiogenic effects. However,in view of the high cost of this therapy, its possible side effects and the relatively benign course of the disease,SSAs should be reserved to specific subsets of "high risk patients", i.e., those patients with multifocal or recurrent GCs. Indeed, it is reasonable that, after the development of a gastric neuroendocrine neoplasm in patients with a chronic predisposing condition(such as CAG), other enterochromaffin-like cells can undergo neoplastic proliferation, being chronically stimulated by hypergastrinemia. Therefore, definite indications to SSAs treatment should be established in order to avoid the undertreatment or overtreatment of GCs.展开更多
Malignant neoplasms of the appendix are rare and represent less than 1% of gastrointestinal cancers.Goblet cell carcinoids(GCC) tumors are a distinctive group of heterogeneous appendiceal neoplasm that exhibit unique ...Malignant neoplasms of the appendix are rare and represent less than 1% of gastrointestinal cancers.Goblet cell carcinoids(GCC) tumors are a distinctive group of heterogeneous appendiceal neoplasm that exhibit unique clinical and pathologic features.This review focuses on the current diagnostic procedures,pathogenesis,possible signaling mechanisms and treatment options for GCC.Perspectives for future research are discussed.The tumor likely arises from pluripotent intestinal epithelial crypt base stem cells.Previous findings of Notch signaling as a tumor suppressor in Neuroendocrine tumors may have a similar role in this tumor too.Loss of Notch signaling may be the driver mutation with other successive downstream mutations likely favors them into progressing and behavior similar to poorly differentiated adenocarcinoma with minimal neuroendocrine differentiation.A multidisciplinary approach is suggested for optimal outcomes.Surgery remains the main treatment modality.Simple appendectomy may be sufficient in early stages while right hemicolectomy is recommended for advanced tumors.Cytoreductive surgery with heated intraperitoneal chemotherapy may improve survival in a select few with metastatic peritoneal disease.These tumors have an unpredictable behavior even in early stages and local recurrence and delayed metastases may be seen.Lifelong surveillance is warranted.展开更多
It is often difficult to evaluate the grade of malignancy and choose an appropriate treatment for colorectal carcinoids in clinical settings. Although tumor size and depth of invasion are evidently not enough to strat...It is often difficult to evaluate the grade of malignancy and choose an appropriate treatment for colorectal carcinoids in clinical settings. Although tumor size and depth of invasion are evidently not enough to stratify the risk of this rare tumor, the present guidelines or staging systems do not mention other clinicopathological variables. Recent studies, however, have shed light on the impact of lymphovascular invasion on the outcome of colorectal carcinoids. It has been revealed that the presence of lymphovascular invasion was among the strongest risk factors for metastasis along with tumor size and depth of invasion. Furthermore, tumors smaller than 1 cm, within submucosal invasion and without lymphovascular invasion, carry minimal risk for metastasis with 100% 5-year survival in the studies from Japan as well as from the USA. This would suggest that these tumors could be curatively treated by endoscopic resection or transanal local excision. On the other hand, colorectal carcinoids with either lymphovascular invasion or tumor size larger than 1 cm carry the risk for metastasis equivalent to adenocarcinomas. Therefore, it should be emphasized that histological examination of lymphovascular invasion is mandatory in the specimens obtained by endoscopic resection or transanal local excision, as this would provide useful information for determining the need for additional radical surgery with regional lymph node dissection. Although the present guidelines or TNM staging system do not mention the impact of lymphovascular invasion, this would be among the next promising targets in order to establish better guidelines and staging systems, particularly in early-stage colorectal carcinoids.展开更多
We report a case of multiple duodenal, pancreatic, and gastric carcinoids. A 67-year old woman was admitted to our hospital for treatment of a duodenal carcinoid. Laboratory tests revealed that the patient was associa...We report a case of multiple duodenal, pancreatic, and gastric carcinoids. A 67-year old woman was admitted to our hospital for treatment of a duodenal carcinoid. Laboratory tests revealed that the patient was associated with macrocytic anemia and hypergastrinemia, and type A gastritis was shown by gastrofiberscopy. During surgery, another tumor was incidentally found in the head of the pancreas. The tumors in the duodenum and pancreas were completely excised by pancreatoduodenectomy and immunohistologically diagnosed as gastrin-and serotonin-producing carcinoids, respectively. Pathological examination revealed that in addition to the grossly found carcinoids, there were subclinical carcinoids, one of which was an endocrine cell micronest, located in the stomach and duodenum. The tumors in the duodenum, pancreas, and stomach showed different characteristics from one another morphologically and immunochemically. Although no definitive evidence has been obtained, some sort of genetic anomaly may have been involved in this case, and hypergastrinemia due to duodenal gastrinoma may induce multiple gastric carcinoids.展开更多
BACKGROUND: Malignant gastric carcinoids are often ac-companied with liver metastasis synchronously or meta-chronously. Because of the slow growth rate of carcinoids,patients with metastatic tumors can undergo resecti...BACKGROUND: Malignant gastric carcinoids are often ac-companied with liver metastasis synchronously or meta-chronously. Because of the slow growth rate of carcinoids,patients with metastatic tumors can undergo resection forpotential cure or for symptom palliation. This study wasdesigned to evaluate the clinicopathologic characteristicsand the diagnosis and management of malignant gastriccarcinoids.METHODS: Seven patients with malignant gastric carci-noids admitted to our hospital between 1990 and 2002 werefollowed up and reviewed retrospectively.RESULTS: Liver metastases were found in all the patients,of whom 3 had lesions simultaneously and the other 4 hadlesions postoperatively. More than 2 lesions were found inall these patients, except a solitary liver lesion in one. Fol-low-up showed two patients died within 2 months, threepatients in 20, 25 and 32 months after operation respective-ly, and the other two have been surviving for more than 5and 3 years respectively.CONCLUSIONS: Malignant gastric carcinoids have a highmetastatic tendency to the liver. Surgical treatment in com-bination with other therapeutic approaches can significantlyprolong the survival rate of the patients.展开更多
AIM:To determine the incidence and clinico-patho-logical profile of appendiceal carcinoids in a cohort of patients undergoing emergency appendicectomies for clinically suspected acute appendicitis in Sharjah,Unit-ed A...AIM:To determine the incidence and clinico-patho-logical profile of appendiceal carcinoids in a cohort of patients undergoing emergency appendicectomies for clinically suspected acute appendicitis in Sharjah,Unit-ed Arab Emirates(UAE).METHODS:The study included the retrospective data of 964 patients operated for clinically suspected acute appendicitis,and the resected specimens were received at Al-Qasmi Hospital(Sharjah)from January 2010 to December 2010.The data of the patients who were histologically reported to have carcinoid tumors of the appendix were extensively evaluated for the patient’s demographics,indication for surgery,surgical pro-cedure,tumor localization in the appendix,diameter of the lesion,concomitant appendicitis,immunohisto-chemistry studies and clinical follow-up.RESULTS:Out of the 964 patients included in the study,9(0.93%)were found to have appendiceal car-cinoids.The mean age reported was 28.7 years with a male to female ratio of 2:1.Eight tumors were located near the tip of the appendix with a mean diameter of 3.3 mm,while the remaining one was near the proximal end of the appendix.All the cases were associated with concomitant suppurative appendicitis.In seven report-ed cases,tumors were confined to the muscular layer while in one case each there was an extension to the serosa and mesoappendix,respectively.All tumors were found to be positive for chromogranin A,synaptophysin and neuron-specific enolase on immunohistochemistry but negative for cytokeratin-7.None of the patients developed recurrence or any reportable complications in the short follow-up period(12-26 mo)that was ar-ranged as a six-monthly re-evaluation by abdominal ultrasonography.CONCLUSION:Our study found a higher incidence of appendiceal carcinoids in patients undergoing emer-gency appendectomy for acute appendicitis in Sharjah,UAE compared to two previous studies from the Persian Gulf region.Interestingly,tumors were found to be more commonly in young males,which is in contrast to previous studies.Moreover,all the tumors were positive for common neuroendocrine markers.展开更多
From 1984 to 1990, six patients with histologically and endocrinologically proven ectopic ACTH syndrome were treated in our department. The lesion in five patients was clinically evident, but in the other was occult. ...From 1984 to 1990, six patients with histologically and endocrinologically proven ectopic ACTH syndrome were treated in our department. The lesion in five patients was clinically evident, but in the other was occult. All lesions were located within the chest. Four were thvmic carcinoid and the other two were bronchial carcinoids. Most of the patients had typical clinical manifestations of Cushing’s syndrome. Laboratory tests including histopathological examination confirmed the diagnosis of ectopic ACTH syndrome. The treatment consisted of surgical removal of the mass supplemented by radiotherapy. The results showed that after treatment all patients had satisfactory remission. Two bronchial carcinoid patients have been living for 40 and 88 months respectively without recurrence. Among 4 thymic carcinoid patients, only one has been living with no tumor for 34 months. One patient had recurrence and the other 2 died 32 and 50 months after the treatment respectively. However, the symptoms of two thymic carci展开更多
Minute(<5mm)and small(5-10mm)rectal carcinoids discovered during colonoscopy are generally considered to be non-aggressive,and the management and surveillance of patients with this entity are usually limited.We pre...Minute(<5mm)and small(5-10mm)rectal carcinoids discovered during colonoscopy are generally considered to be non-aggressive,and the management and surveillance of patients with this entity are usually limited.We present the case of a 61-year-old Chinese female with multiple sub-5mmcarcinoid tumours in the rectum without any computed tomography(CT)evidence of lymph node or distant metastases.She underwent an ultra-low anterior resection for a sessile rectal polyp with the histological appearance of a moderately differentiated adenocarcinoma.Seven foci of minute carcinoids in the rectum and perirectal lymph node metastastic spread from the carcinoid tumours were also discovered on histopathology.There were no lymph node metastases originating from adenocarcinoma.This case report and review of the literature suggests that minute rectal carcinoids are at risk of metastasizing and that these patients should be investigated for lymph node and distant metastatic spread with CT and somatostatin receptor scintigraphy or its equivalent,as this would influence prognosis and surgical management of these patients.Findings relating to lymphovascular invasion,perineural invasion,high Ki-67,mitotic rate,depth of tumour invasion,central ulceration,multifocal tumours and size are useful in predicting metastases and may be used in scoring tools.Size alone is not a good predictor of metastastic spread.展开更多
Rectal neuroendocrine tumors(r-NETs)are the second most common type of neuroendocrine tumor in the gastrointestinal tract,with an increase in incidence in the last decades.They are low-grade tumors and,given their low...Rectal neuroendocrine tumors(r-NETs)are the second most common type of neuroendocrine tumor in the gastrointestinal tract,with an increase in incidence in the last decades.They are low-grade tumors and,given their low risk of meta-stasis,current guidelines recommend endoscopic resection for small lesions.The GATIS predicting score,proposed by Zeng et al,represents an innovative model designed to predict individualized survival outcomes for patients with r-NETs,analyzing the relationship between clinicopathological features and patient prog-noses.The authors identified tumor grade,T stage,tumor size,age,and progno-stic nutritional index as key prognostic factors,demonstrating that the GATIS Score provides a more accurate prognosis assessment compared to the World Health Organization classification or the tumor-node-metastasis staging system.Nevertheless,further larger prospective studies are necessary,and the scientific community's efforts in this context should be directed toward developing interna-tional multicentric prospective studies,with the ultimate aim of accurately de-fining and understanding the behavior of these conditions.展开更多
Neuroendocrine tumors are a rare cancer,with those arising in gastric tissue even less commonly.With increasing recognition through endoscopy,these tumors are diagnosed in more patients each year.As a rare and growing...Neuroendocrine tumors are a rare cancer,with those arising in gastric tissue even less commonly.With increasing recognition through endoscopy,these tumors are diagnosed in more patients each year.As a rare and growing entity,our understanding of these tumors,the way we characterize them,and treatment are changing rapidly.Thus,we sought to provide an updated review of pathology and management,highlighting the latest guidelines and evidence for surgical treatment.Much of the general treatment paradigm is from consensus guidelines put forth by the European Neuroendocrine Tumor Society and the North American Neuroendocrine Tumor Society;however,future research is needed to help guide further surgical decision-making around intermediate grade and intermediate size type Ⅲ tumors,as well as systemic therapies in the perioperative and nonoperative settings for high-grade tumors.展开更多
Neuroendocrine neoplasms are a group of tumors with heterogenous malignancy that evolve from neuroendocrine cells,most frequently in the gastrointestinal tract and in the lung.The latest 2021 World Health Organization...Neuroendocrine neoplasms are a group of tumors with heterogenous malignancy that evolve from neuroendocrine cells,most frequently in the gastrointestinal tract and in the lung.The latest 2021 World Health Organization(WHO)classification of lung tumors defines neuroendocrine neoplasms of the lung as an independent group of tumors,including typical and atypical neuroendocrine tumors and small cell and large cell neuroendocrine carcinomas.Although the overall nomenclature is essentially unchanged from the fourth WHO classification,there are several clinically relevant updates.In this review article,we discuss the epidemiological,clinical,diagnostic,therapeutic and prognostic features of these fascinating neoplasms,including the latest insights,current challenges and future perspectives.展开更多
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 recogni...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.展开更多
AIM:To describe disease characteristics and treatment modalities in a group of rare patients with metastatic gastric carcinoid type 1(GCA1).METHODS:Information on clinical,biochemical,radiological,histopathological fi...AIM:To describe disease characteristics and treatment modalities in a group of rare patients with metastatic gastric carcinoid type 1(GCA1).METHODS:Information on clinical,biochemical,radiological,histopathological findings,the extent of the disease,as well as the use of different therapeutic modalities and the long-term outcome were recorded.Patients’data were assessed at presentation,and thereafter at 6 to 12 monthly intervals both clinically and biochemically,but also endoscopically and histopathologically.Patients were evaluated for the presence of specific symptoms;the presence of autoimmune disorders and the presence of other gastrointestinal malignancies in other family members were also recorded.The evaluation of response to treatment was defined using established WHO criteria.RESULTS:We studied twenty consecutive patients with a mean age of 55.1 years.The mean follow-up period was 83 mo.Twelve patients had regional lymph node metastases and 8 patients had liver metastases.The primary tumor mean diameter was 20.13±10.83mm(mean±SD).The mean Ki-67 index was 6.8%±11.2%.All but one patient underwent endoscopic or surgical excision of the tumor.The disease was stable in all but 3 patients who had progressive liver disease.All patients remained alive during the follow-up period.CONCLUSION:Metastatic GCA1 carries a good overall prognosis,being related to a tumor size of≥1 cm,an elevated Ki-67 index and high serum gastrin levels.展开更多
Western countries are seeing a constant decline in the incidence of Helicobacter pylori-associated gastritis, coupled with a rising epidemiological and clinical impact of autoimmune gastritis. This latter gastropathy ...Western countries are seeing a constant decline in the incidence of Helicobacter pylori-associated gastritis, coupled with a rising epidemiological and clinical impact of autoimmune gastritis. This latter gastropathy is due to autoimmune aggression targeting parietal cells through a complex interaction of auto-antibodies against the parietal cell proton pump and intrinsic factor, and sensitized T cells. Given the specific target of this aggression, autoimmune gastritis is typically restricted to the gastric corpus-fundus mucosa. In advanced cases, the oxyntic epithelia are replaced by atrophic(and metaplastic) mucosa, creating the phenotypic background in which both gastric neuroendocrine tumors and(intestinal-type) adenocarcinomas may develop. Despite improvements in our understanding of the phenotypic changes or cascades occurring in this autoimmune setting, no reliable biomarkers are available for identifying patients at higher risk of developing a gastric neoplasm. The standardization of autoimmune gastritis histology reports and classifications in diagnostic practice is a prerequisite for implementing definitive secondary prevention strategies based on multidisciplinary diagnostic approaches integratingendoscopy, serology, histology and molecular profiling.展开更多
New insights emerged last decade that enriched our knowledge regarding the biological behavior of appendiceal neuroendocrine tumors(NETs),which range from totally benign tumors less than 1cm to goblet cell carcinomas ...New insights emerged last decade that enriched our knowledge regarding the biological behavior of appendiceal neuroendocrine tumors(NETs),which range from totally benign tumors less than 1cm to goblet cell carcinomas which behave similarly to colorectal adenocarcinoma.The clinical implication of that knowledge reflected to surgical strategies which also vary from simple appendicectomy to radical abdominal procedures based on specific clinical and histological characteristics.Since the diagnosis is usually established post-appendicectomy,current recommendations focus on the early detection of:(1)the subgroup of patients who require further therapy;(2)the recurrence based on the chromogranin a plasma levels;and(3)other malignancies which are commonly developed in patients with appendiceal NETs.展开更多
文摘Gastric carcinoids(GCs),which originate from gastric enterochromaffin-like(ECL) mucosal cells and account for 2.4% of all carcinoids,are found increasingly in the course of upper gastrointestinal tract endoscopy.Current nosography includes those occurring in chronic conditions with hypergastrinemia,as the type 1 associated with chronic atrophic gastritis,and the type 2 associated with Zollinger-Ellison syndrome in multiple endocrine neoplasia type 1,and type 3,which is unrelated to hypergastrinemia and is frequently malignant,with distant metastases.The optimal clinical approach to GCs remains to be elucidated,depending upon type,size and number of carcinoids.While there is agreement concerning the treatment of type 3 carcinoids,for types 1 and 2,current possibilities include simple surveillance,endoscopic polypectomy,surgical excision,associated or not with surgical antrectomy,or total gastrectomy.Moreover,the recent introduction of somatostatin analogues represents a therapeutic option of possibly outstanding relevance.
文摘AIM: To assess the results of endoscopic mucosal re-section with a ligation device (EMR-L) combined with three dimensional endoscopic ultrasonography (3D-EUS) using an ultrasonic probe for rectal carcinoids. In addition, diagnosis of the depth and size of lesions by EUS was evaluated. METHODS: Between January 2003 and March 2007, 20 patients underwent EMR-L with 3D-EUS using an ultrasonic probe (group A). 3D-EUS was combined with EMR-L at the time of injection of sterile physiological saline into the submucosal layer. For comparison, 14 rectal carcinoids that had been treated by EMR-L with-out 3D-EUS between April 1998 and December 2002 were evaluated as historical controls (group B). EUS was conducted for all of the patients before treatment to evaluate tumor diameter and depth of invasion. The percentage of complete resection and the verti-cal resection margin were compared between the two groups. RESULTS: The depth of invasion upon histopathologi-cal examination was in complete agreement with the pre-operative fi ndings by EUS. The tumor diameter de-termined by EUS approximated that found in the tissue samples. There were no signifi cant differences in the gender, tumor sites or tumor diameters between the two groups. The rate of complete resection for groups A and B was 100% and 71%, respectively (P < 0.05). The vertical resection margin of group A was longer than that of group B. CONCLUSION: EMR-L is effective as an endoscopictreatment for rectal carcinoids. In combination with 3D-EUS, safe and complete resection is further as-sured.
文摘AIM： To investigate the expression of cyclin-dependent kinase inhibitors p21 and p27 in gastric well differentiated endocrine tumors （GWDET） （ECLocell carcinoids）.METHODS： The expressions of p21 and p27 were examined immunhistochemically in endoscopic biopsy specimens from 16 patients matching the diagnostic criteria of GWDET. Percentage of positive nuclear staining either weak or strong was noted. The association of immunoexpressions with age, gender, tumor localization, multifocality and accompanying chronic atrophic gastritis, neuroendocrine cell hyperplasia （NEH）, neuroendocrine dysplasia （NED）, intestinal metaplasia （IM）, Ki-67 proliferation index and clinical outcome were also evaluated.RESULTS： All cases expressed p27 with a mean expression score of 43.6%, while 31.3% of the cases showed any p21 expression, p21 and p27 immunoexpressions were significantly correlated with each other （P 〈 0.01）, and the p21-expressing group had higher p27 expression scores （68% vs 22%）. p21 and p27 expressions were lower in women, in non-atrophic mucosa and cases whose tumors were located somewhere other than fundus without submucosal extension. On contrary, p21 and p27 expressions were higher in males and the patients with submucosal extension and atrophic gastritis. Cases presenting lower p27 scores had solitary tumors showing neither NEH-NED nor IM. Despite, cases with lower p21 expression presented multifocal tumors accompanied by NEH-NED. However, no correlation of p21 and p27 expressions was found with age and Ki-67 expression.CONCLUSION： p27 is widely expressed in GWDETs, while p21 expression is sparse and observed in two thirds of the cases. Loss of p21 and p27 expressions may be correlated with different carcinoid tumor subtypes; however,more studies are needed to assess the role of these prospective markers in gastrointestinal endocrine tumors.
文摘An estimated 25% to 30% of all neuroendocrine tumors (NETs) have their origin in the bronchial tree and into the lungs. Although lung NETs account for less than 1% of all pulmonary malignancies, the incidence of these neoplasms has risen precipitously since the mid 1970s. Currently, according to the 2004 World Health Organization categorization, these tumors are separated into 4 subtypes characterized by increasing biologic aggressiveness: low-grade typical carcinoid (TC), intermediate-grade atypical carcinoid (AC), high-grade large-cell neuroendocrine carcinoma (LCNEC) and small-cell carcinoma (SCLC). Surgery is the treatment of choice for typical and atypical carcinoid lung NETs with loco-regional disease. At diagnosis up to 64% of patients with atypical carcinoid lung NETs present with lymph node metastases, and 5-year survival ranges from 61% to 88%. In contrast, lymph node metastases are present in fewer than 15% of typical carcinoid lung NETs, and 5-year survival exceeds 90%. To date, there is no recognized standard of treatment for advanced carcinoid lung NETs. In recent years only two trials reported intriguing results regarding lung NETs: a phase 2 retrospective study of dacarbazine derivative temozolomide and the phase 3, RADIANT-2 trial in advanced NETs. Successful management requires a multidisciplinary team management. This review is restricted to typical/atypical NETs.
文摘AIM: To assess the therapeutic value of endoscopic mucosal resection (EMR) under micro-probe ultrasound guidance for rectal carcinoids less than 1 cm in diameter. METHODS: Twenty-one patients pathologically diagnosed with rectal carcinoids following colonoscopy in our hospital from January 2007 to November 2012 were included in this study. The patients consisted of 14 men and 7 women, with a mean age of 52.3 ± 12.2 years (range: 36-72 years). The patients with submucosal tumors less than 1 cm in diameter arising from the rectal and muscularis mucosa detected by micro-probe ultrasound were treated with EMR and followed up with conventional endoscopy and micro-probe ultrasound. RESULTS: All of the 21 tumors were confirmed by micro-probe ultrasound as uniform hypoechoic masses originating from the rectal and muscularis mucosa, without invasion of muscularis propria and vessels, and less than 1 cm in diameter. EMR was successfully completed without bleeding, perforation or other complications. The resected specimens were immunohistochemically confirmed to be carcinoids. Patients were followed up for one to two years, and no tumor recurrence was reported. CONCLUSION: EMR is a safe and effective treatment for rectal carcinoids less than 1 cm in diameter.
文摘Gastric carcinoids(GCs) are classified as: type Ⅰ,related to hypergastrinemia due to chronic atrophic gastritis(CAG), type Ⅱ, associated with Zollinger-Ellison syndrome in multiple endocrine neoplasia type 1, and type Ⅲ, which is normogastrinemic. The management of type-Ⅰ gastric carcinoids(GC1s) is still debated,because of their relatively benign course. According to the European Neuroendocrine Tumor Society guidelines endoscopic resection is indicated whenever possible;however, it is not often feasible because of the presence of a multifocal disease, large lesions, submucosal invasion or, rarely, lymph node involvement. Therefore,somatostatin analogs(SSAs) have been proposed as treatment for GC1 s in view of their antisecretive,antiproliferative and antiangiogenic effects. However,in view of the high cost of this therapy, its possible side effects and the relatively benign course of the disease,SSAs should be reserved to specific subsets of "high risk patients", i.e., those patients with multifocal or recurrent GCs. Indeed, it is reasonable that, after the development of a gastric neuroendocrine neoplasm in patients with a chronic predisposing condition(such as CAG), other enterochromaffin-like cells can undergo neoplastic proliferation, being chronically stimulated by hypergastrinemia. Therefore, definite indications to SSAs treatment should be established in order to avoid the undertreatment or overtreatment of GCs.
文摘Malignant neoplasms of the appendix are rare and represent less than 1% of gastrointestinal cancers.Goblet cell carcinoids(GCC) tumors are a distinctive group of heterogeneous appendiceal neoplasm that exhibit unique clinical and pathologic features.This review focuses on the current diagnostic procedures,pathogenesis,possible signaling mechanisms and treatment options for GCC.Perspectives for future research are discussed.The tumor likely arises from pluripotent intestinal epithelial crypt base stem cells.Previous findings of Notch signaling as a tumor suppressor in Neuroendocrine tumors may have a similar role in this tumor too.Loss of Notch signaling may be the driver mutation with other successive downstream mutations likely favors them into progressing and behavior similar to poorly differentiated adenocarcinoma with minimal neuroendocrine differentiation.A multidisciplinary approach is suggested for optimal outcomes.Surgery remains the main treatment modality.Simple appendectomy may be sufficient in early stages while right hemicolectomy is recommended for advanced tumors.Cytoreductive surgery with heated intraperitoneal chemotherapy may improve survival in a select few with metastatic peritoneal disease.These tumors have an unpredictable behavior even in early stages and local recurrence and delayed metastases may be seen.Lifelong surveillance is warranted.
文摘It is often difficult to evaluate the grade of malignancy and choose an appropriate treatment for colorectal carcinoids in clinical settings. Although tumor size and depth of invasion are evidently not enough to stratify the risk of this rare tumor, the present guidelines or staging systems do not mention other clinicopathological variables. Recent studies, however, have shed light on the impact of lymphovascular invasion on the outcome of colorectal carcinoids. It has been revealed that the presence of lymphovascular invasion was among the strongest risk factors for metastasis along with tumor size and depth of invasion. Furthermore, tumors smaller than 1 cm, within submucosal invasion and without lymphovascular invasion, carry minimal risk for metastasis with 100% 5-year survival in the studies from Japan as well as from the USA. This would suggest that these tumors could be curatively treated by endoscopic resection or transanal local excision. On the other hand, colorectal carcinoids with either lymphovascular invasion or tumor size larger than 1 cm carry the risk for metastasis equivalent to adenocarcinomas. Therefore, it should be emphasized that histological examination of lymphovascular invasion is mandatory in the specimens obtained by endoscopic resection or transanal local excision, as this would provide useful information for determining the need for additional radical surgery with regional lymph node dissection. Although the present guidelines or TNM staging system do not mention the impact of lymphovascular invasion, this would be among the next promising targets in order to establish better guidelines and staging systems, particularly in early-stage colorectal carcinoids.
文摘We report a case of multiple duodenal, pancreatic, and gastric carcinoids. A 67-year old woman was admitted to our hospital for treatment of a duodenal carcinoid. Laboratory tests revealed that the patient was associated with macrocytic anemia and hypergastrinemia, and type A gastritis was shown by gastrofiberscopy. During surgery, another tumor was incidentally found in the head of the pancreas. The tumors in the duodenum and pancreas were completely excised by pancreatoduodenectomy and immunohistologically diagnosed as gastrin-and serotonin-producing carcinoids, respectively. Pathological examination revealed that in addition to the grossly found carcinoids, there were subclinical carcinoids, one of which was an endocrine cell micronest, located in the stomach and duodenum. The tumors in the duodenum, pancreas, and stomach showed different characteristics from one another morphologically and immunochemically. Although no definitive evidence has been obtained, some sort of genetic anomaly may have been involved in this case, and hypergastrinemia due to duodenal gastrinoma may induce multiple gastric carcinoids.
文摘BACKGROUND: Malignant gastric carcinoids are often ac-companied with liver metastasis synchronously or meta-chronously. Because of the slow growth rate of carcinoids,patients with metastatic tumors can undergo resection forpotential cure or for symptom palliation. This study wasdesigned to evaluate the clinicopathologic characteristicsand the diagnosis and management of malignant gastriccarcinoids.METHODS: Seven patients with malignant gastric carci-noids admitted to our hospital between 1990 and 2002 werefollowed up and reviewed retrospectively.RESULTS: Liver metastases were found in all the patients,of whom 3 had lesions simultaneously and the other 4 hadlesions postoperatively. More than 2 lesions were found inall these patients, except a solitary liver lesion in one. Fol-low-up showed two patients died within 2 months, threepatients in 20, 25 and 32 months after operation respective-ly, and the other two have been surviving for more than 5and 3 years respectively.CONCLUSIONS: Malignant gastric carcinoids have a highmetastatic tendency to the liver. Surgical treatment in com-bination with other therapeutic approaches can significantlyprolong the survival rate of the patients.
文摘AIM:To determine the incidence and clinico-patho-logical profile of appendiceal carcinoids in a cohort of patients undergoing emergency appendicectomies for clinically suspected acute appendicitis in Sharjah,Unit-ed Arab Emirates(UAE).METHODS:The study included the retrospective data of 964 patients operated for clinically suspected acute appendicitis,and the resected specimens were received at Al-Qasmi Hospital(Sharjah)from January 2010 to December 2010.The data of the patients who were histologically reported to have carcinoid tumors of the appendix were extensively evaluated for the patient’s demographics,indication for surgery,surgical pro-cedure,tumor localization in the appendix,diameter of the lesion,concomitant appendicitis,immunohisto-chemistry studies and clinical follow-up.RESULTS:Out of the 964 patients included in the study,9(0.93%)were found to have appendiceal car-cinoids.The mean age reported was 28.7 years with a male to female ratio of 2:1.Eight tumors were located near the tip of the appendix with a mean diameter of 3.3 mm,while the remaining one was near the proximal end of the appendix.All the cases were associated with concomitant suppurative appendicitis.In seven report-ed cases,tumors were confined to the muscular layer while in one case each there was an extension to the serosa and mesoappendix,respectively.All tumors were found to be positive for chromogranin A,synaptophysin and neuron-specific enolase on immunohistochemistry but negative for cytokeratin-7.None of the patients developed recurrence or any reportable complications in the short follow-up period(12-26 mo)that was ar-ranged as a six-monthly re-evaluation by abdominal ultrasonography.CONCLUSION:Our study found a higher incidence of appendiceal carcinoids in patients undergoing emer-gency appendectomy for acute appendicitis in Sharjah,UAE compared to two previous studies from the Persian Gulf region.Interestingly,tumors were found to be more commonly in young males,which is in contrast to previous studies.Moreover,all the tumors were positive for common neuroendocrine markers.
文摘From 1984 to 1990, six patients with histologically and endocrinologically proven ectopic ACTH syndrome were treated in our department. The lesion in five patients was clinically evident, but in the other was occult. All lesions were located within the chest. Four were thvmic carcinoid and the other two were bronchial carcinoids. Most of the patients had typical clinical manifestations of Cushing’s syndrome. Laboratory tests including histopathological examination confirmed the diagnosis of ectopic ACTH syndrome. The treatment consisted of surgical removal of the mass supplemented by radiotherapy. The results showed that after treatment all patients had satisfactory remission. Two bronchial carcinoid patients have been living for 40 and 88 months respectively without recurrence. Among 4 thymic carcinoid patients, only one has been living with no tumor for 34 months. One patient had recurrence and the other 2 died 32 and 50 months after the treatment respectively. However, the symptoms of two thymic carci
文摘Minute(<5mm)and small(5-10mm)rectal carcinoids discovered during colonoscopy are generally considered to be non-aggressive,and the management and surveillance of patients with this entity are usually limited.We present the case of a 61-year-old Chinese female with multiple sub-5mmcarcinoid tumours in the rectum without any computed tomography(CT)evidence of lymph node or distant metastases.She underwent an ultra-low anterior resection for a sessile rectal polyp with the histological appearance of a moderately differentiated adenocarcinoma.Seven foci of minute carcinoids in the rectum and perirectal lymph node metastastic spread from the carcinoid tumours were also discovered on histopathology.There were no lymph node metastases originating from adenocarcinoma.This case report and review of the literature suggests that minute rectal carcinoids are at risk of metastasizing and that these patients should be investigated for lymph node and distant metastatic spread with CT and somatostatin receptor scintigraphy or its equivalent,as this would influence prognosis and surgical management of these patients.Findings relating to lymphovascular invasion,perineural invasion,high Ki-67,mitotic rate,depth of tumour invasion,central ulceration,multifocal tumours and size are useful in predicting metastases and may be used in scoring tools.Size alone is not a good predictor of metastastic spread.
文摘Rectal neuroendocrine tumors(r-NETs)are the second most common type of neuroendocrine tumor in the gastrointestinal tract,with an increase in incidence in the last decades.They are low-grade tumors and,given their low risk of meta-stasis,current guidelines recommend endoscopic resection for small lesions.The GATIS predicting score,proposed by Zeng et al,represents an innovative model designed to predict individualized survival outcomes for patients with r-NETs,analyzing the relationship between clinicopathological features and patient prog-noses.The authors identified tumor grade,T stage,tumor size,age,and progno-stic nutritional index as key prognostic factors,demonstrating that the GATIS Score provides a more accurate prognosis assessment compared to the World Health Organization classification or the tumor-node-metastasis staging system.Nevertheless,further larger prospective studies are necessary,and the scientific community's efforts in this context should be directed toward developing interna-tional multicentric prospective studies,with the ultimate aim of accurately de-fining and understanding the behavior of these conditions.
文摘Neuroendocrine tumors are a rare cancer,with those arising in gastric tissue even less commonly.With increasing recognition through endoscopy,these tumors are diagnosed in more patients each year.As a rare and growing entity,our understanding of these tumors,the way we characterize them,and treatment are changing rapidly.Thus,we sought to provide an updated review of pathology and management,highlighting the latest guidelines and evidence for surgical treatment.Much of the general treatment paradigm is from consensus guidelines put forth by the European Neuroendocrine Tumor Society and the North American Neuroendocrine Tumor Society;however,future research is needed to help guide further surgical decision-making around intermediate grade and intermediate size type Ⅲ tumors,as well as systemic therapies in the perioperative and nonoperative settings for high-grade tumors.
文摘Neuroendocrine neoplasms are a group of tumors with heterogenous malignancy that evolve from neuroendocrine cells,most frequently in the gastrointestinal tract and in the lung.The latest 2021 World Health Organization(WHO)classification of lung tumors defines neuroendocrine neoplasms of the lung as an independent group of tumors,including typical and atypical neuroendocrine tumors and small cell and large cell neuroendocrine carcinomas.Although the overall nomenclature is essentially unchanged from the fourth WHO classification,there are several clinically relevant updates.In this review article,we discuss the epidemiological,clinical,diagnostic,therapeutic and prognostic features of these fascinating neoplasms,including the latest insights,current challenges and future perspectives.
文摘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.
文摘AIM:To describe disease characteristics and treatment modalities in a group of rare patients with metastatic gastric carcinoid type 1(GCA1).METHODS:Information on clinical,biochemical,radiological,histopathological findings,the extent of the disease,as well as the use of different therapeutic modalities and the long-term outcome were recorded.Patients’data were assessed at presentation,and thereafter at 6 to 12 monthly intervals both clinically and biochemically,but also endoscopically and histopathologically.Patients were evaluated for the presence of specific symptoms;the presence of autoimmune disorders and the presence of other gastrointestinal malignancies in other family members were also recorded.The evaluation of response to treatment was defined using established WHO criteria.RESULTS:We studied twenty consecutive patients with a mean age of 55.1 years.The mean follow-up period was 83 mo.Twelve patients had regional lymph node metastases and 8 patients had liver metastases.The primary tumor mean diameter was 20.13±10.83mm(mean±SD).The mean Ki-67 index was 6.8%±11.2%.All but one patient underwent endoscopic or surgical excision of the tumor.The disease was stable in all but 3 patients who had progressive liver disease.All patients remained alive during the follow-up period.CONCLUSION:Metastatic GCA1 carries a good overall prognosis,being related to a tumor size of≥1 cm,an elevated Ki-67 index and high serum gastrin levels.
基金Supported by A grant from the Italian Association for Cancer Research(partly,AIRC Regional grant 2008 No.6421)published under the auspices of the Healthy Stomach Initiative(HIS)
文摘Western countries are seeing a constant decline in the incidence of Helicobacter pylori-associated gastritis, coupled with a rising epidemiological and clinical impact of autoimmune gastritis. This latter gastropathy is due to autoimmune aggression targeting parietal cells through a complex interaction of auto-antibodies against the parietal cell proton pump and intrinsic factor, and sensitized T cells. Given the specific target of this aggression, autoimmune gastritis is typically restricted to the gastric corpus-fundus mucosa. In advanced cases, the oxyntic epithelia are replaced by atrophic(and metaplastic) mucosa, creating the phenotypic background in which both gastric neuroendocrine tumors and(intestinal-type) adenocarcinomas may develop. Despite improvements in our understanding of the phenotypic changes or cascades occurring in this autoimmune setting, no reliable biomarkers are available for identifying patients at higher risk of developing a gastric neoplasm. The standardization of autoimmune gastritis histology reports and classifications in diagnostic practice is a prerequisite for implementing definitive secondary prevention strategies based on multidisciplinary diagnostic approaches integratingendoscopy, serology, histology and molecular profiling.
文摘New insights emerged last decade that enriched our knowledge regarding the biological behavior of appendiceal neuroendocrine tumors(NETs),which range from totally benign tumors less than 1cm to goblet cell carcinomas which behave similarly to colorectal adenocarcinoma.The clinical implication of that knowledge reflected to surgical strategies which also vary from simple appendicectomy to radical abdominal procedures based on specific clinical and histological characteristics.Since the diagnosis is usually established post-appendicectomy,current recommendations focus on the early detection of:(1)the subgroup of patients who require further therapy;(2)the recurrence based on the chromogranin a plasma levels;and(3)other malignancies which are commonly developed in patients with appendiceal NETs.
