Jun Soga

Carcinoids of the Rectum: An Evaluation of 1271 Reported Cases

The present study was conducted to evaluate the current status of rectal carcinoids from multiple systemic aspects, based on extensive information provided by 1271 cases cited in 465 international articles published since 1912. Each case report was carefully read, computerized, and analyzed by the gut-pancreatic endocrinoma analysis system (Niigata Registry). To avoid case duplication, cases without individual identification, such as the age and sex of the patient, and those with identical clinical and laboratory data and institutes of source, were excluded. Where appropriate, selected cases from an overall gastrointestinal (GI) series consisting of 4461 cases similarly documented in the same Registry were referred to for comparison. The representative characteristics of rectal carcinoids consisted of a male preponderance, small-sized tumors of 10 mm or less at detection, predominant submucosal invasion with a relatively high incidence of metastases, a high incidence of hematogenous spread, a predominant histology of the B-type growth pattern, a low rate of silver reactivity, the infrequent association of carcinoid syndrome, and a relatively high rate of mortality within 5 years after removal of the lesions.

Classification of tumours

Tumours are classified according to the most differentiated cells with the exception of carcinomas where a few tumour cells show neuroendocrine differentiation. In this case these cells are regarded as redifferentiated tumour cells, and the tumour is not classified as neuroendocrine. However, it is now clear that normal neuroendocrine cells can divide, and that continuous stimulation of such cells results in tumour formation, which during time becomes increasingly malignant. To understand tumourigenesis, it is of utmost importance to recognize the cell of origin of the tumour since knowledge of the growth regulation of that cell may give information about development and thus possible prevention and prophylaxis of the tumour. It may also have implications for the treatment. The successful treatment of gastrointestinal stromal tumours by a tyrosine kinase inhibitor is an example of the importance of a correct cellular classification of a tumour. In the future tumours should not just be classified as for instance adenocarcinomas of an organ, but more precisely as a carcinoma originating from a certain cell type of that organ.

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.

Gastric Carcinoids:A Statistical Evaluation of 1094 Cases Collected from the Literature

Gastric carcinoids are a rare gut endocrinoma, and only a few series dealing with limited aspects have been published. This study evaluates the present status and characteristics of gastric carcinoids in a statistically reliable series of 1094 cases that were carefully evaluated, computerized, and analyzed by the “Gut-Pancreatic Endocrinoma Analyzing System.” Routine statistical analysis was carried out on 1011 patients, excluding 83 with atypical carcinoids, focusing on clinical manifestations, location, depth, and size of the lesions in relation to metastases, immunohistochemistry, carcinoid syndrome, serotonin activity, electron microscopy, multicarcinoid complex with type A gastritis, and postoperative outcome. A tumor size of 20 mm or less comprised 60.8% of the series, with a metastasis rate of 15.1%, and depth of invasion to the submucosa occupied 53.8%, with a metastasis rate of 13.2%. Carcinoid syndrome was encountered in 4.0% of the patients. Elevated serotonin activity was detected in 22.3% overall and in 67.7% of the patients with carcinoid syndrome (P<0.01). Multicarcinoid complex with type A gastritis was detected in 140 of 347 patients with multicarcinoid complex, and 97.1% had associated lesions in the nonantral regions of the stomach. A comparative evaluation between patients with and without type A gastritis indicated a number of significant differences including male to female ratio, age distribution, location, tumor size, depth of invasion, metastasis, and prognosis.

Superficial spreading carcinoma of the esophagus

Superficial spreading type of carcinoma of the esophagus was defined as lesions with an intramucosal extension of carcinoma 20 mm or more from the main lesion. Eleven (6.1%) of 179 cases were thus selected for this investigation. These cases were further divided into two groups: Group A, consisting of four cases (2.2%) with the main lesion confined to the submucosa, representing a relatively early stage; and Group B, consisting of seven cases (3.9%) with the main lesion invading the muscular layer or deeper. One of the most characteristic features in the four cases belonging to Group A was an unexpectedly high incidence of lymphatic permeation and lymph node metastases leading to a poor prognosis. Another feature that may be important, particularly for surgeons performing esophagectomy, was the difficulty in deciding the proximal resection line of the esophagus because the boundaries between involved and uninvolved portions were frequently indistinguishable in this particular pathologic entity, not only in Group A but in Group B.

Total gastrectomy for gastric cancer. Clinical considerations on 431 cases

On the basis of the invasive and metastatic natures of gastric cancer, 431 cases of total gastrectomy were analyzed from the standpoint of surgical treatments. Histologic scrutinization showed that 83% of the cases (199/241) had lymph node metastasis, and 26% of the lymph nodes (2,226/8,698) were involved. In cancer of the upper stomach, lymph node involvement became suddenly widespread in extent and high in rate, both for the cases and for the lymph nodes with the serosal invasion by the primary lesions. In addition, a serial sectioning technique from the splenic hilus through the splenic artery region disclosed that latent lymph node metastasis evident only on histologic scrutinization consisted of 62% of the involved lymph nodes. These rather unexpected results suggest that, in most cases with advanced cancer in the upper stomach or of a diffuse form, a total gastrectomy combined with a splenectomy and caudal hemipancreatectomy would be a necessary surgical procedure.

Role of preoperative administration of Bleomycin and radiation in the treatment of esophageal cancer

The preoperative use of Bleomycin (BLM) alone or combined with irradiation in the treatment of esophageal cancer was evaluated in 58 patients who underwent surgical removal of the lesion for the past three and a half years. Histologic study showed such preoperative treatment is effective in inducing favorable changes in neoplastic cells in 69 per cent (40/58) of the primary lesions and in a significant number of involved lymph nodes of the second or the third groups. The study clearly suggests that preoperative Bleomycin administration combined with irradiation may be an useful adjunct preoperative procedure in esophageal cancer.

Pancreatic endocrinomas: A statistical analysis of 1,857 cases

A total of 1857 cases of pancreatic endocrinomas and related pathological disorders producing gut-pancreatic hormones were collected from the world literature and were statistically analyzed and evaluated. The entire series in the present study consisted primarily of histologically confirmed islet cell tumors, but included 30 cases of vasoactive intestinal peptide (VIP)-producing neurogenic tumors and 54 cases of islet hyperplasia, the former being excluded from the systematic evaluation. The series consisted of seven groups: (1) gastrinomas/Zollinger-Ellison syndrome (ZES), (2) somatostatinomas, (3) glucagonomas/diabetes-dermatitis syndrome (DDS), (4) insulinomas/hypoglycemic syndrome (HGS), (5) vipomas/watery diarrhea hypokalemia achlorhydria (WDHA) syndrome, (6) pancreatic polypeptide (PP)-producing tumors (PPomas), and (7) miscellaneous endocrinomas. The statistical analysis dealt mainly with the location, male/female ratio, age distribution, clinical and pathological features, multiplicity, and malignant nature of pancreatic endocrinomas. The delineating of 52 PPomas in this series, and confirmation of the tumor entity by radioimmunoassay and immunocytochemical procedures, were matters of special emphasis in this study.

Difference in calcium metabolism following Billroth-I and Billroth-II procedures for gastric and duodenal ulcers.

There have been 7 patients with postoperative osteomalacia in our series of 500 patients who had a gastrectomy for gastric or duodenal ulcers. All seven of these patients had a Billroth-II type gastrojejunostomy or esophagojejunostomy which caused food to bypass the duodenum and the upper part of the jejunum, and six of these patients showed milk intolerance and had diarrhea on food other than cows milk. From this finding, it may be surmised that patients are predisposed to osteopenia after gastrectomy due to disorder in the process of calcium absorption and they develop osteomalacia when treated with the Billroth-II procedure, showing milk intolerance and diarrhea on food other than cows milk.

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.