Mineralocorticoid receptor blocker eplerenone improves endothelial function and inhibits Rho-associated kinase activity in patients with hypertension.

Hypertension is associated with endothelial dysfunction and activated Rho-associated kinases (ROCKs). The purpose of this study was to evaluate the effects of the selective mineralocorticoid receptor blocker, eplerenone, on endothelial function and ROCK activity in patients with hypertension. The study was carried out over 48 weeks in 60 untreated patients with hypertension who were randomly assigned to eplerenone, nifedipine, and losartan groups. We evaluated the effects of each treatment on flow-mediated vasodilation (FMD) and ROCK activity in peripheral leukocytes. Eplerenone increased FMD and decreased leukocyte ROCK activity. Nifedipine decreased ROCK activity but did not alter FMD. Losartan increased FMD but did not alter ROCK activity. Hypotensive effects were similar in the three groups, as was nitroglycerin-induced vasodilation during the follow-up period. There were no significant differences between the groups with respect to other parameters. The study results show that eplerenone improves endothelial function and inhibits ROCK activity in patients with essential hypertension.

Endocrinocarcinomas (carcinoids and their variants) of the duodenum. An evaluation of 927 cases.

This study was undertaken to supplement our previous analysis of 635 duodenal carcinoids to give both wider and different viewpoints on a larger series of duodenal endocrinocarcinomas, and to provide up-to-date clinicopathologic information regarding these neoplasms. A total of 927 cases of such neoplasms of the duodenum were collected from the Niigata Registry for gut-pancreatic endocrinomas, consisting of the carcinoid group with 897 cases, 857 typical carcinoids and 40 atypical varieties, and the variant group with 30 remaining endocrinocarcinomas expressed by various terminology. Significant statistical differences between these two groups were evident in various aspects: in sites of tumor growth, aggressiveness of invasion to the extra-duodenal structures, rates and sites (liver, lymph nodes and bone) of metastases, average tumor-size, immunohistochemistry of gastrin and serotonin, rates of recurrence, five-year survival rates and others. In addition, a close similarity between these two groups was noted in several aspects of histology, histochemistry and immunohistochemistry, rendering the variant group in a member of the carcinoid family. Regarding the carcinoid group in comparison with that in other organs may be summarized as follows: a reasonable male/female ratio of 1.39, a reasonable average age of 55.9 years, a high typical/atypical ratio of 21.4, a relatively small average tumor-size of 17.7 mm, a relatively low metastasis rate of 27.4%, a high histologic B-type dominance of 75.5%, a high postoperative survival rate of 83.3% and a reasonable incidence of the carcinoid syndrome of 3.1%.

Primary endocrinomas (carcinoids and variant neoplasms) of the gallbladder. A statistical evaluation of 138 reported cases.

This study was carried out to obtain extensive information on carcinoids (the carcinoid group) and related variant endocrinomas (the variant group) of the gallbladder, and to statistically analyze their characteristics from various clinicopathologic aspects. A total of 138 cases were collected from the international sources, 101 belonging to the carcinoid group and 37 to the variant group. The first group consisted of 81 cases of typical and 20 atypical carcinoids. Comparative evaluation was attempted mainly between the carcinoid and variant groups, and occasionally between the typical and atypical carcinoid series when statistical significance was suspected. The carcinoid group showed a statistically significant difference from the variant group by exhibiting a younger average age (61.7 years vs 69.7 years: P<0.01), a higher incidence of associated cholelithiasis (87.3% vs 56.0%: P<0.01), a higher incidence of small tumors 50 mm or less (85.2% vs 52.9%: P<0.01), a smaller average tumor-size (29.6 mm vs 58.7 mm: P<0.01), a lower rate of metastases (40.7% vs 70.6%: P<0.05), a higher immunoreactivity rate of chromogranin (100.0% vs 66.7%: P<0.01), a lower immunoreactivity rate of gastrin (23.8% vs 70.6%: P<0.01), and a higher five-year survival rate (60.4% vs 21.3%: P<0.0005). Significant differences in various clinicopathological aspects confirmed between the carcinoid group and the variant group suggested that endocrine carcinomas of these two groups perform a different clinical pattern, represented most clearly by postoperative outcomes. These groupings are decided on the basis of histologic patterns, namely, well to poorly differentiated endocrine carcinomas (typical to atypical carcinoids) and undifferentiated or anaplastic variants of other endocrine carcinomas. The basic criteria for such classification of these endocrine carcinomas based on international agreements are required.

Carcinoids and their variant endocrinomas. An analysis of 11842 reported cases.

Endocrinocarcinomas consisting of carcinoids and their variant carcinomas with endocrine features are neoplasms of relatively rare occurrence but have often been reported in many countries and regions of the world. The largest series of 13715 cases from the United States was published in 2003. A total number of 11842 reported cases of endocrinocarcinomas from the Niigata Registry were divided into two groups: the carcinoid group (n = 10804) with the typical (n = 9430) and the atypical (n = 1374) series and the variant group (n = 1038). These cases came from 64 countries and reports were written in 17 different languages. They were statistically evaluated for comparison between the two groups or series in various aspects, including gender and age, tumor-size, rate of metastases, immunohistochemistry, and survival after curative resection. In the carcinoid group, more frequent cases were found in the digestive system (64.2%) than in the extradigestive system (35.8%). Organ distribution of carcinoid cases exhibited the most frequent site to be the respiratory system (19.8%), followed by the rectum (15.0%), jejunoileum (12.0%), stomach (11.4%), appendix (9.6%) and duodenum (8.3%). An extremely small number of cases (less than 0.7%) were found in the middle ear, testicle, kidney, and several others. The highest rate of metastases was noted in the ileocecum (75.3%), followed by the jejunoileum (65.2%), pancreas (64.2%), and larynx (61.4%). Small carcinoids with invasion confined to the mucosa and submucosa, indicated an unexpectedly high metastasis rate of 13.8% for lesions 20 mm or less, and 10.0% for those 10 mm or less, and 6.1% for those 5 mm or less. The carcinoid syndrome was found to occur at the rate of 7.7% of overall 11057 cases reported between 1953 and 2002, with the highest incidence of 28.8% in the 5-year period between 1963 and 1967, gradually decreasing down to 3.7% in the last 5 years. The 5-year survival rate after curative resection of lesions showed a significant difference between the carcinoid group and the variant group (82.0% vs 41.8%: P < 0.0001). In the former group, the 5-year survival rate showed a significant difference between cases with or without metastases (61.4% vs 95.7%: P < 0.0001). In the latter group, the 5-year survival rate was 74.5% for cases without metastases and 24.1% for those with metastases (P < 0.0001). The highest 5-year survival rate in the carcinoid group was noted in the ovary (93.6%), followed by the liver (92.6%), the respiratory system (89.7%), the appendix (89.5%), and the rectum (85.4%), while poor 5-year survival rates were recorded in the pancreas (43.2%), the esophagus (43.5%) and the larynx (47.6%). It should be emphasized that there is a significant statistical difference in many aspects between the carcinoid group and the variant group. The present study confirms that the malignant nature of these endocrine tumors is well reflected in their metastasis rates, even in small lesions with submucosal invasion, resulting in the 5-year survival rates of a significant difference among the groups or series.

Laryngeal endocrinomas (carcinoids and relevant neoplasms): analysis of 278 reported cases.

This study was carried out to provide extensive information obtained from statistical analysis of laryngeal endocrinomas for the use of investigators working in this particular research field. A total of 278 patients with both typical and atypical varieties of carcinoids, and with small/oat cell carcinomas (SCC/OCC) exhibiting a confirmed endocrine nature were statistically evaluated, and the significance in various clinicopathologic aspects among these three types of such endocrine neoplasms of the larynx was compared. A statistically significant difference between two groups of typical carcinoid and atypical variety was evident only in a few items such as rates of metastases, positive CEA, and multisecretory activity, while a significant difference between the carcinoid groups and SCC/OCC group was demonstrated in numerous areas, among others, e.g. 1) in the overall rates of metastases and at the sites of involvement, 2) in Grimelius argyrophilia, 3) in immunohistochemical demonstration of positive chromogranin, CEA, calcitonin and multisecretory activity, and 4) in the 5-year survival rates. Such a definite difference between the carcinoid groups and SCC/OCC group suggested an apparently different characteristic nature present between these two series of neoplasms. The necessity of an international agreement regarding diagnostic criteria for typical carcinoids and atypical varieties was in particular emphasized from a viewpoint of an exceptionally high incidence of laryngeal atypical carcinoids in comparison to such neoplasms in other organs.

Primary hepatic endocrinomas (carcinoids and variant neoplasms). A statistical evaluation of 126 reported cases.

This study was undertaken to evaluate the statistical results of a large collected series of primary hepatic endocrinomas including carcinoids from extensive clinicopathologic aspect, and to provide the information to investigators engaged in this particular field of research. Primary hepatic endocrinomas variously termed as endocrine cell carcinoma (ECC), neuroendocrine carcinoma (NEC), carcinoid, and other carcinomas with endocrine components (CECs), have been rarely reported in literature. A total of 126 reported cases were registered in the Niigata Registry for gut-pancreatic endocrinomas. They consisted of a carcinoid group with typical carcinoids (n=82) and atypical carcinoids (n=19) and another group with other variant endocrinomas, briefly expressed as the variant group (n=25) in this study. The number of females was larger than that of males in the carcinoid group (M/F=0.58) and reversely males were predominant in the variant group (M/F=1.78). The average age was considerably older in the carcinoid group as compared to that in the variant group (53.9 years vs 48.3 years). The carcinoid group (either typical, atypical or both) showed a significant lower value than the variant group in metastasis rates in the large (over 50 mm) tumor series (43.3% vs 75.0%: P<0.05), and higher than the latter in serotonin positivity demonstrated by immunohistochemistry (37.0% vs 11.1%). While no significant difference was present between the two groups, cases with large tumors over 50 mm were found at a high rate (P<0.01) in approximately three fourths of each group, i.e. 76 out of a total of 100 cases recorded, and the liver was more often involved by metastasis than lymph nodes in the carcinoid group (32.7% vs 19.8%: P<0.05) though no significant difference was noted between these two sites in the variant group. The five-year survival rates calculated by the Kaplan-Meier method showed better results in the carcinoid group than in the variant group but with no statistically significant difference (92.4% vs 68.1%). A close similarity found in many aspects of the two groups suggested endocrinomas in the present study apparently belong to one family of CECs or briefly "carcinoid family". Regarding the more detailed statistical analyses, further accumulation of well-documented cases is needed.

Gut-endocrinomas (carcinoids and related endocrine variants) of the uterine cervix: an analysis of 205 reported cases.

This study was carried out statistically to evaluate the present situation of carcinoids and related endocrine variants in the uterine cervix. A total of 205 patients who had been reported on in world-wide literature were divided into two groups; one, as a carcinoid group, consisting of 81 patients with carcinoids, 49 typical and 32 atypical, and the others, as an endocrine carcinoma (ECC) group, including 124 patients with other remaining endocrine carcinomas variously expressed up to date. A statistical comparison in multiple factors was attempted between these two groups. A statistically significant difference between them was demonstrated in immunochemistry for chromogranin (p<0.05), serotonin (p<0.01), and CEA (p<0.01), but not regarding average age, clinical manifestations, tumor-size categorization, rates of metastases, sites of metastases, argyrophilia or argent affinity, and postoperative five-year survival rates, though the latter disclosed a statistically significant difference (p<0.05) only between the two groups of typical and atypical carcinoids. The results of analysis in the present study disclosing no statistically significant differences in various aspects between the two groups of carcinoids and the remaining endocrine carcinomas strongly suggest that the considerable extent of confusion produced by various different types of terminology for carcinoids and related endocrine variants should be solved by extensive evaluation and discussion on an international scale, and that diagnostic criteria and simplified classification acceptable for these neoplasms are to be established not only for those of the uterine cervix but also for those of all other organs including the digestive system based on a universally acceptable concept for these neoplasms originating in non-endocrine organs.

Statistical analysis of endocrine granule size in gastrointestinal carcinoids.

Regarding the size of endocrine granules in endocrine neoplasms including carcinoids, most authors have reported only the range of granule diameters, and few studies on detailed morphometry of granule sizes have been documented. The statistically comparative study of endocrine granule sizes among such neoplasms, therefore, presented many difficulties. In the present study, we investigated more detailed findings on the endocrine granule sizes by using statistical analyses of diameters of numerous (n > 200 from each tumor) endocrine granules measured randomly throughout the cytoplasm in 18 gastrointestinal carcinoids. The measured data were analyzed statistically to obtain the histogram, distribution curve, mean value, and standard deviation of granule diameters in each carcinoid. It was disclosed by the analyses that all rectal carcinoids possessed uniformly small endocrine granules in contrast to gastric and duodenal carcinoids, which showed wide distribution of granule sizes, having significantly greater diameters than those in the rectal carcinoid series. The correlation between endocrine granule sizes and producing hormone(s) was, however, not confirmed.

Gut-endocrinomas (carcinoids and related endocrine variants) of the breast: an analysis of 310 reported cases.

The purpose of this study was to analyze the present status of gut-endocrinomas (carcinoids and related endocrine variants) of the breast, an extremely rare site for primary growth of such neoplasms, and to provide precise and reliable information concerning these neoplasms on varying clinicopathological aspects for investigators engaged in relevant research fields. A total of 310 cases presented in this analysis consisted of 196 carcinoids, 102 typical and 94 atypical, and 114 related endocrine variants; in the last group, the expression of "breast carcinoma with (neuro-) endocrine differentiation" was often used without referring to the term "carcinoid." A statistical evaluation was performed on most occasions based on a comparison among three groups of typical carcinoids, atypical carcinoids and related endocrine variants, or between the former two series of carcinoids and the third series of endocrine carcinomas. Statistically significant differences between the groups of carcinoids and endocrine carcinomas were recognized in terms of average age, tumor size categories of < or = 20 mm and 21-50 mm, rates of metastases, and positive neuron-specific enolase (NSE) immunohistochemistry. Contrary to our expectations no statistically significant difference between these two groups was evident in terms of overall average tumor size, Grimelius argyrophilia for endocrine nature, or postoperative 5-year survival rates in curative resection cases. It seems important to establish more precise diagnostic criteria for "endocrine carcinomas" from the viewpoint of a certain possibility that some of these neoplasms may belong to the atypical carcinoid group.

Carcinoids of the ovary: an analysis of 329 reported cases.

This evaluation was undertaken to supply precise and reliable detailed information to investigators actively working in carcinoid and related gynecological research fields. A statistical evaluation was performed on 329 cases of ovarian carcinoid registered in the Niigata Registry where world-wide information of gut-pancreatic endocrinomas has been maintained by a computer-analyzing system. Cases without individual identification or those recorded in groups were excluded. The evaluation was carried out mainly by a comparison between two groups of cases with cystic teratoma/dermoid (Group A) and those without such lesions (Group B). The former group consisted of 189 cases (57.4%) and the latter of 140 (42.6%). Statistically significant differences between these two groups were recognized in tumor size (44.7 mm vs 89.8 mm), rate of metastases (5.8% vs 22.1%), rate of hepatic involvement (2.1% vs 15.0%), incidence of associated carcinoid syndrome (13.8% vs 22.9%) and 5-year survival rate (93.7% vs 84.0%). Insular type and trabecular type carcinoids were recorded at an almost equal rate of one fourth ranging between 22% and 26% in either group. Another significant difference in the incidence of carcinoid syndrome was evident between the series of insular type and trabecular type carcinoids (38.9% vs 7.8%). The present evaluation on ovarian carcinoids disclosed definite, statistically significant differences in various clinical and pathophysiologic aspects between Group A and Group B, as well as between insular type and trabecular type histologic structures.

Evaluation of 342 cases of mediastinal/thymic carcinoids collected from literature: a comparative study between typical carcinoids and atypical varieties.

This study is aimed to provide extensive and useful information based on an analysis of a large and reliable series of cases regarding mediastinal/thymic carcinoids, both typical and atypical. It also serves to assist investigators to improve their research activities in this particular field. In the present study, 342 patients (3.8%) with mediastinal/thymic carcinoids from amongst a total series of 8,970 patients with carcinoids, registered in the Niigata Registry for gut-pancreatic endocrinomas, were analyzed to clarify their detailed clinicopathological characteristics. Added to an analysis of mediastinal/thymic series including a comparison between typical and atypical carcinoid varieties, another comparative study was performed between the present series and a bronchopulmonary series. Mediastinal/thymic carcinoids may be briefly characterized by 1) no significant difference in major factors statistically demonstrable between typical carcinoids and atypical varieties, 2) a male preponderance, 3) difficult (delayed) preoperative diagnosis, 4) a high rate of metastasis, 5) a large tumor size on average (delayed detection), 6) a low rate of the carcinoid syndrome, 7) a high rate of association of the Cushing syndrome, and 8) low postoperative survival rates.

Dedifferentiation of neoplastic cells in medullary thyroid carcinoma: report of a case.

We report herein the unusual case of a man who was diagnosed as having sporadic medullary thyroid carcinoma (MTC) at the age of 29 years, and subsequently followed up for a period of 18 years. A total thyroidectomy with radical neck dissection was initially performed, followed by a stable interval of 16 years with regional metastases. He then developed widely disseminated metastases resulting in death within 2 years at the age of 47 years. While the neoplastic tissue from localized metastases in the soft tissue of the neck expressed strong immunohistochemical positivity to calcitonin (CT), calcitonin gene-related peptide, carcinoembryonic antigen, neuron-specific enolase, and chromogranin A during the stable interval, extremely weakened immunoreactivity to those markers was observed in samples from the disseminated metastases in the subcutaneous tissue after his clinical deterioration. Furthermore, only a few neoplastic cells in specimens obtained at postmortem sampling exhibited a weak response to CT. Ultrastructurally, the characteristic secretory granules in the neoplastic cells decreased remarkably in number, consistent with the immunohistochemical findings. These granules also diminished in diameter and intracytoplasmic small lumina and intercellular clefts with microvilli, interpreted as an attribute of anaplastic thyroid carcinomas, were frequently observed in tissues obtained after his clinical deterioration or at postmortem sampling. These cytological changes might represent dedifferentiation of the neoplastic cells or the anaplastic transformation of MTC.

Bronchopulmonary carcinoids: An analysis of 1,875 reported cases with special reference to a comparison between typical carcinoids and atypical varieties.

This study was undertaken to provide investigators working in this particular research field with extensive and useful basic information based on an analysis of a large reliable series of cases regarding tracheal and bronchopulmonary carcinoids and their atypical varieties. A statistical evaluation was carried out which included a total of 1,875 patients with tracheal and bronchopulmonary carcinoids; these were divided into two series, one of 1,595 patients with typical carcinoids and the other of 280 with atypical varieties. These two series were compared regarding various aspects, which included the male to female ratio, age distribution, clinical manifestations, successful preoperative diagnosis, diagnostic accuracy of representative procedures, sites of involvement, tumor size distribution, metastases, carcinoid syndrome, serotonin activity in patients with or without the syndrome, immunohistochemistry, electron microscopy, and postoperative prognosis of the patients. The comparative analyses between the two series disclosed statistically significant differences (p<0.01) regarding various viewpoints; among others, such a difference was proved in the average age, sites of involvement in the lung (central or peripheral), rates and sites of metastases, adrenocorticotrophic hormone (ACTH) production, the association rate of the carcinoid syndrome, and postoperative 5-year and 10-year survival rates (93.3% and 82.1% for the typical carcinoid series versus 68.8% and 58.6% for the atypical variety series: p<0.0001). The postoperative 5-year and 10-year survival rates in the other two groups of patients with or without metastases were likewise calculated and showed a statistically significant difference (72.8% and 52.8% for the former versus 98.3% and 95.4% for the latter: p<0.0001).

Carcinoid syndrome: a statistical evaluation of 748 reported cases.

No statistical evaluation of patients with carcinoid syndrome in a reliable number of cases has been available in the past 35 years. To update our knowledge about the syndrome, we have evaluated from various clinicopathologic viewpoints a large series of patients with the syndrome reported up to date. The data of 748 patients with the syndrome were collected from 8876 carcinoid patients reported in the literature and analyzed by the Gut-Pancreatic Endocrinoma Analyzing System (the Niigata Registry). The results are summarized as follows. 1) The patients with the syndrome had a tendency to be older than those without it. 2) The incidence of the syndrome was 8.4% of 8876 carcinoid patients. 3) Serotonin activities were extremely high in patients with the syndrome as compared to those without it (91.7% versus 26.6%). 4) The rate of metastases was higher in patients with the syndrome than in those without it (84.8% versus 29.2%), and higher in the liver than in lymph nodes among patients with the syndrome (73.4% versus 37.4%). 5) Flushing and carcinoid heart as most specific clinical manifestations of the syndrome were recorded at 78.3% and 17.4%, respectively. 6) The 5-year survival rate after resection of primary lesions was 76.0% of 304 patients with the syndrome, lower in patients with digestive carcinoids than in those with extradigestive lesions (67.2% versus 88.7%). It is expected that the results obtained in the present evaluation on patients with carcinoid syndrome will provide investigators active in this specialized field with useful and extensive information for their future activities.

A classification of problems regarding gut endocrinomas (carcinoids and relevant neoplasms).

In the field of gut endocrinomas (carcinoids and relevant neoplasms), several classifications have been internationally accepted and utilized at varying frequency. The basis of the concepts regarding gut endocrinomas from which these classifications have been proposed were drawn from the different aspects. These included embryology, histologic growth patterns, histochemistry including silver impregnations, electron microscopic morphology of endocrine secretory granules, endocrine cell types and histologic morphology along with functional characteristics, supplemented by immunohistochemical features. Due to continuous progress being made in this particular field of research and the many new discoveries made by pioneering investigators, the concepts of gut endocrinomas have been modified and revised during such long history of the research activities. This study aims to re-evaluate these classifications in relation to the concepts of gut endocrinomas, and to select and supply rearranged classifications that may be easily utilized for practical purposes. This study also proposes a comprehensive overview of histogenesis in the gut endocrinoma group. This consists of typical carcinoids and their atypical variants taken in relation to the carcinomatous group including ordinary carcinomas and their variants with endocrine elements. Special emphasis is given to the point that there is a gradual transition, one without a definite boundary between these tumors.

Somatostatinoma/inhibitory syndrome: a statistical evaluation of 173 reported cases as compared to other pancreatic endocrinomas.

Somatostatin is known to inhibit the secretory release of other peptide hormones. Somatostatinomas associated either with or without somatostatinoma (inhibitory) syndrome are rare neoplasms among gut-pancreatic endocrinomas. Collected from international literature, this study aimed to perform a statistical analysis on 173 patients with somatostatinoma/inhibitory syndrome. The evaluation further attempted to provide investigators in this particular field of research with extensive and precise information on the present situation of somatostatinoma. The 173 patients consisted of 81 with pancreatic somatostatinomas and 92 with extrapancreatic somatostatinomas. Most of the latter were found to have originated in the duodenum and may be termed as carcinoid somatostatinoma. Where data were considered to be adequate, a comparative study was carried out between two groups, pancreatic and duodenal, each consisting of 81 patients. A statistically significant difference between these two groups was found in the incidence of inhibitory syndrome (18.5% versus 2.5%) and von Recklinghausen's disease (1.2% versus 43.2%), large size of tumor (>20 mm) (85.5% versus 41.4%), multisecretory activities (33.3% versus 16.3%), and presence of psammoma bodies (2.5% versus 49.4%). There was no statistically significant difference in the rate of metastases and malignancy between the two groups. The average postoperative 5-year survival rate was 75.2% in 90 patients overall, 59.9% in 44 with metastases and 100.0% in 46 without metastases. Compared with the other pancreatic endocrinomas, including PPomas, glucagonomas, vipomas, gastrinomas, and insulinomas, somatostatinomas were characterized by the low rate of the relevant syndrome and multiple endocrine neoplasia syndrome type 1. There was a low rate of multiplicity, and a high incidence of psammoma bodies in the duodenal group particularly with von Recklinghausen's disease. A high rate of malignancy was recorded, resulting in a low postoperative survival rate of patients with metastases. In conclusion, somatostatinomas exhibited characteristic features quite different from those of the other pancreatic endocrinomas regarding multiple points.

Carcinoids of the colon and ileocecal region: a statistical evaluation of 363 cases collected from the literature.

The colon and ileocecal region are rare sites of origin for gastrointestinal carcinoids. This study evaluates the present status and characteristics of carcinoids of these particular sites in a statistically reliable number of cases and offers fundamental information for future analysis and treatment of these neoplasias. A total of 363 cases of colonic and ileocecal carcinoids were collected from international literature and evaluated in the computer analyzing system. For the final evaluation, 279 cases with sufficient information, consisting of 203 colonic and 76 ileocecal carcinoids, were selected for analysis. In addition, 69 cases of atypical varieties in identical sites were studied for a comparison of 5-year survival rates with the 279 ordinary colonic and ileocecal carcinoids. The characteristic features of colonic and ileocecal carcinoids included: 1) a female preponderance and older age group in the ileocecal carcinoids; 2) a higher incidence of carcinoids in the cecum as compared to those of the rest of the colon followed by the ileocecal region; 3) a high incidence of palpable abdominal tumors resulting from a tendency of the tumors to be large (89.7% were over 2 cm); 4) a high incidence of metastases (61.3%); 5) a high incidence of Grimelius argyrophilia (100.0%) and argentaffin cell type (85.7%) in ileocecal carcinoids; 6) a low detection rate of serotonin in immunohistochemical (66.7%) and laboratory (68.7%) evaluation; and 7) a low postoperative 5-year survival rate (40.5% by the crude calculation method and 65.3% by the Kaplan-Meier method). The present statistical evaluation disclosed a considerable delay in detecting colonic and ileocecal carcinoids resulting in extensive and aggressive surgical treatments and poor postoperative outcomes.

Tumor recurrence in patients with early gastric cancer: a clinicopathologic evaluation.

We conducted a retrospective study on 711 patients with early gastric cancer. Twenty-two patients (4.0%) developed recurrent disease and 21 died of recurrence during this study. One hundred and sixty-three patients died of unrelated or unknown causes. The recurrence patterns of 22 patients were as follows: hematogeneous metastasis to the liver in 11 patients, peritoneal dissemination in 3, recurrence in the remnant stomach in 3, and in the distant lymphonodes in 1. The mean survival period of patients with recurrent disease was 50.4 months, and 7 of these patients (31.8%) died more than 5 years after surgery. A retrospective clinicopathologic evaluation of the 22 patients and 526 patients without recurrence revealed significant differences between the two groups with respect to mean age at the time of surgery (62.5 years in the recurrent group vs 57.3 years in the nonrecurrent group), tumor size (41.2 vs 30.6 mm), depth of invasion (submucosal cancer: 19 vs 256), lymphnode metastasis (11 vs 48), lymphatic (11 vs 89) and venous (7 vs 18) invasion, and operative curability (curability B: 8 vs 48). Three patients with intramucosal cancer who died of hematogenous and/or peritoneal recurrence within 7 years after surgery had neither lymphnode metastasis nor lymphatic or venous invasion, suggesting that new techniques are needed for prediction of recurrent disease in patient with early gastric cancer.

The gastrinoma/Zollinger-Ellison syndrome: statistical evaluation of a Japanese series of 359 cases.

The diagnostic modalities and management of gastrinoma/Zollinger-Ellison syndrome (ZES) have been markedly modified and improved over the past 15 years. To evaluate the present status of this disease, in terms of various clinicopathologic features, we collected 359 Japanese cases of gastrinoma/ZES from the literature. We found a decreasing incidence (from 74.7% in 1965-1980 to 34.2% in 1981-1995) of multiple surgeries and a decreasing rate (from 94.3% in 1965-1980 to 83.5% in 1981-1995) of ZES associated with gastrinoma. There was an increasing rate (from 12.6% in 1965-1980 to 48.9% in 1981-1995) of correct preoperative diagnosis. (All these differences were significant; P < 0.01). In 1981-1995, there was a high incidence (51. 1%) of small tumors (20 mm or less) and a high rate (39.5%) of metastases, and a relatively favorable postoperative outcome (10-year survival rate of 63.7%); P < 0.05. The diagnosis and treatment of gastrinoma/ZES have been markedly improved by increased rates of curative surgery, and more favorable postoperative outcomes will be expected in decades to come.

Statistical evaluation of 2001 carcinoid cases with metastases, collected from literature: a comparative study between ordinary carcinoids and atypical varieties.

This study aimed at obtaining a better understanding of the malignant characteristics of carcinoids (gut endocrinomas) of the digestive system. After excluding cases with no possible individual identification as for age and sex, 2001 carcinoid cases with metastases among 5647 of the digestive system computerized in the Niigata Registry were thus subject to the present analysis. These cases were divided into two groups: [A] 1719 with ordinary carcinoid histology and [B] 282 with atypical varieties including argyrophil (endocrine) cell carcinomas, small/oat cell carcinomas of endocrine type, composite carcinoid-adenocarcinoma varieties and other neuroendocrine tumors. In many aspects, a comparative analysis demonstrated statistical differences between [A] and [B]: average age (55.7 vs 60.1), the rates of metastases (34.4% vs 55.6%), the association of carcinoid syndrome (21.4% vs 2.8%), tumor size 20mm or less (42.2% vs 22.5%), depth of invasion down to the submucosa (21.6% vs 11.7%) and transmural invasion (34.3% vs 47.7%), immunohistochemistry of neuron-specific enolase (86.5% vs 66.7%), chromogranin (86.1% vs 67.6%), vasointestinal polypeptides, ACTH and alpha-fetoprotein, and the 5-year survival rate (61.4% vs 17.9%). No statistical differences between these two groups were found in the male to female ratio, serotonin activities and Grimelius argyrophilia. Although no generally acceptable definite criteria and definition for atypical carcinoid varieties have yet established, neoplasias of this category seem to have a wide range of histological, histochemical, immunohistochemical, ultrastructural and biochemical features that may mostly be placed in between ordinary carcinoids and ordinary carcinomas.