Masaaki Izukura

Neurotensin Stimulates Growth of Colonic Mucosa in Young and Aged Rats

Neurotensin, a tridecapeptide widely distributed in the gut, stimulates growth of small bowel mucosa in young and aged rats. In the present study, the effect of long-term neurotensin administration on the growth of colonic mucosa was examined in young (2-month-old) and aged (24-month-old) rats. Subcutaneous injections of saline (control) or neurotensin (300 micrograms/kg) in gelatin were given to the groups of rats every 8 hours for 10 days. During treatment, all rats were maintained on a regular chow diet. Rats were killed on day 11; the entire colon was removed, mucosa was scraped and weighed, and DNA, RNA, and protein contents were determined. Neurotensin induced growth of colonic mucosa in both age groups. In young rats, neurotensin increased weight and DNA, RNA, and protein contents of colonic mucosa. The ratio of DNA content, an index of cellular hyperplasia, was increased significantly in the neurotensin-treated young rats compared with age-matched controls, indicating an overall increase in mucosal cellularity. In the aged rats, growth was characterized by an increase in weight and RNA and protein contents, but not DNA content, thus suggesting cellular hypertrophy. These results suggest that neurotensin has an important regulatory function in the growth of colonic mucosa; however, the mode of action, at the cellular level, appears to be different depending on age.

Clinicopathologic study of thyroid carcinoma infiltrating the trachea

Eighteen patients (10 women and 8 men), ranging in age from 37 to 80 years, with thyroid carcinoma infiltrating the trachea comprised this series. Eleven had primary and 7 had recurrent cases. Total laryngectomy was performed in 4 patients, and tracheal resection was carried out followed by end‐to‐end anastomosis in 13 patients. In one patient, reconstruction was done with Navilles artificial trachea after tracheal resection. Eleven patients were alive after 1 year and 8 months to 6 years and 7 months after the operation. This result was significantly better than that of a group of ten patients without resection of the infiltrated trachea (seven patients died within 6 months). Thus, combined resection of the upper airway improved the prognosis of advanced thyroid carcinoma with tracheal infiltration. Histologic examination of surgical specimens demonstrated well‐differentiated carcinoma in seven patients, poorly differentiated carcinoma in seven patients, undifferentiated carcinoma in three patients, and squamous cell carcinoma in one patient. The result showed a higher frequency of poorly differentiated carcinoma than in the control group of 70 patients without tracheal infiltration.

Usefulness of an estimation of physiologic ability and surgical stress (E-PASS) scoring system to predict the incidence of postoperative complications in gastrointestinal surgery

Surgical intervention induces various host responses to maintain homeostasis. When postoperative inflammation is intense and persists for a long time, postoperative complications may occur, sometimes developing into multiple organ failure. Therefore, it is very important to assess surgical stress and predict the risk of morbidity and mortality. Using a new scoring system, an estimation of physiologic ability and surgical stress (E-PASS) scoring system, surgical stress following gastrointestinal surgery was evaluated to assess the feasibility of this scoring system. This system comprises a preoperative risk score (PRS), a surgical stress score (SSS), and a comprehensive risk score (CRS) that is calculated from both the PRS and the SSS. The relationship of the E-PASS score to the incidence of morbidity and mortality was examined. The relationship between the E-PASS score and a sequential organ failure (SOFA) score was also evaluated. The CRS had a significant positive correlation between not only the incidence but also the grade of postoperative complications. Total maximum SOFA score in patients with a CRS of more than 1 was significantly higher than that in patients with a CRS of less than 1. In conclusion, the E-PASS scoring system will be useful for predicting and recognizing the risk of postoperative complications. This scoring system is brief, simple, and reproducible and can be useful in all types of hospitals.

Immunohistochemical Detection of P-glycoprotein in Breast Cancer and Its Significance as a Prognostic Factor.

Overexpression of P-glycoprotein (Pgp) in tumors is one of the major mechanisms which mediates the multidrug resistance (MDR) phenotype. To evaluate the prognostic significance of Pgp in breast cancer, Pgp expression was examined in paraffin-embedded tissue sections of 94 breast cancer specimens by immunohistochemistry. Tissue specimens were obtained by mastectomy without preoperative chemotherapy. UIC2 monoclonal antibody which recognizes an extracellular epitope of human Pgp was employed. Of the 94 breast cancer specimens, 35 (37.2%) were positive for Pgp expression. Pgp expression had no correlation with menopausal or hormone receptor status, axillary lymph node involvement or tumor size. However, a significant correlation was observed between Pgp expression and disease relapse (p = 0.0322). Pgp-positive patients showed a significantly shorter disease-free survival period than Pgp-negative patients by the Kaplan-Meier method (p = 0.0433). These results suggest that immunohistochemical detection of Pgp in breast cancer tissue may have prognostic value after radical operation.

Role of bile and trypsin in the release of cholecystokinin in humans

The influences of (a) intraluminal bile deficiency due to common bile duct obstruction and (b) intraduodenal administration of pooled own bile and bovine trypsin on the plasma cholecystokinin (CCK) response to oral fat (Lipomul) ingestion were investigated in seven patients with periampullary tumors and 10 healthy volunteers. Basal and fat-stimulated plasma CCK levels in the patients were significantly higher than in the normal controls. Intraduodenal administration of pooled own bile at a rate of 100 ml/h significantly suppressed both basal and fat-stimulated CCK secretion. Simultaneous administration of pooled own bile (100 ml/hr) and bovine trypsin (600 mg/hr) caused further significant suppression of fat-stimulated CCK secretion compared with that under bile infusion alone. These results indicate that both intraluminal bile and trypsin exert a negative feedback effect on the release of CCK in humans.

Long-term Follow-up of Gastroplasty in a Patient with Prader-Willi Syndrome

To prevent the development of metabolic disturbances caused by overeating, we performed vertical banded gastroplasty in an adult woman with Prader-Willi syndrome. Her fasting blood sugar (FBS) and urinary sugar excretion (US) decreased during 6 months after the surgery under strict dietary control in the hospital. The insulin response to oral glucose at 6 months after surgery was as good as in the normal controls. A barium meal study in the 11th postoperative month revealed that the staple line was partially ruptured. After this, FBS and US increased, and the glucose tolerance and insulin response worsened. At 24 months, US was still less than preoperative US, and the oral glucose tolerance test showed a better result than before operation. At 29 months, her condition was brought under control with use of Glibenclamide. At 60 months, her FBS and US were at the same level as before operation. She was doing a part-time job. In conclusion, the effect of gastroplasty in preventing worsening of glucose metabolism in a case of Prader-Willi syndrome lasted satisfactorily for 24 months in spite of the partial breakdown of the staple line.

A prospective study on the prognostic significance of urokinase-type plasminogen activator levels in breast cancer tissue

Abstract Urokinase-type plasminogen activator (u-PA), which cleaves plasminogen to yield plasmin, is a serine protease of fibrinolysis and is presumed to play a key role in extracellular proteolysis and facilitate the migration of cancer cells. This study was conducted prospectively to evaluate the prognostic significance of u-PA antigen level in breast cancer tissues. u-PA concentrations in the cytosol of 226 breast cancer tissues were determined prospectively by enzyme-linked immunosorbent assay using cytosol fractions prepared for steroid hormone assay. The median follow-up period of the patients was 60 months. Various prognostic factors were evaluated by univariate analysis or multivariate analysis using the Cox proportional-hazards method. Patients with primary breast cancer containing high levels of u-PA had a significantly shorter disease-free survival than patients with low levels of u-PA antigens. In multivariate analysis, a high level of u-PA was an independent risk factor for disease-free survival, being independent of age, axillary node status, and estrogen receptor status. Among the major prognostic factors, a high u-PA antigen level, lymph node involvement, and a positive estrogen receptor status were the most important for predicting relapse-free survival (P=0.044, P<0.0001, P=0.0039). This first prospective study confirmed the prognostic significance of the u-PA antigen level in association with other major prognostic factors. The results of our present study suggest that u-PA in breast cancer tissue might be involved in breast cancer invasion and metastasis.

Ovarian carcinoma with fistula formation to the sigmoid colon and ileum: report of a case.

We describe herein an extremely rare case of clear cell type ovarian carcinoma resulting in fistula formation into the colon and intestine. The patient was a 61-year-old woman in whom a large tumor with extravasation from the sigmoid colon was found by barium enema examination. The tumor was preoperatively diagnosed as left ovarian cancer by angiography which showed the tumor feeder arising from the left ovarian and uterine arteries.

Role of endogenous somatostatin in postprandial hypersecretion of neurotensin in patients after gastrectomy.

OBJECTIVE The purpose of this report is to elucidate the mechanism of the hypersecretion of neurotensin (NT) after gastrectomy. SUMMARY BACKGROUND DATA NT secretion induced by fat ingestion is increased after pancreatoduodenectomy or distal gastrectomy. The hypersecretion of NT in the patients undergoing resection of the upper gastrointestinal tract is suppressed by an exogenous somatostatin (SST) analog. METHODS We observed simultaneously the secretion of NT and SST in the same patients before and after gastrectomy (n = 7). We also observed the secretion of these hormones induced by intraduodenal (ID) fat infusion in the normal volunteers (n = 6). RESULTS The response of plasma NT to fat ingestion was significantly increased after gastrectomy compared with that before gastrectomy. The response of plasma SST after gastrectomy was significantly suppressed. The response of plasma NT and SST after ID fat infusion in the normal volunteers was similar to the gastrectomized state. CONCLUSION Diminution of SST secretion, probably caused by the lack of SST cells in the distal part of the stomach, may play a role in augmenting NT secretion after gastrectomy.

Simultaneous observation of endocrine and exocrine functions of the pancreas responding to somatostatin in man

Six patients who underwent segmental autotransplantation of the caudal pancreas (SAT) following total pancreatectomy for pancreatic cancer were investigated. The graft was transplanted to the left groin, and pancreatic juice was diverted outside through a polyethylene tube indwelled into the main pancreatic duct. In these SAT patients, the responses of insulin (IRIS) in terms of plasma levels and pancreatic secretion to subcutaneous injections of somatostatin octreotide (Sandostatin: SMS201-995) were simultaneously observed. Four doses (0.039, 0.156, 0.625 and 2.5 micrograms/kg) of SMS201-995 were given on separate days. As a control, saline was injected subcutaneously. Standard liquid test meal was given 1 h after the subcutaneous injection. The basal plasma IRI were significantly decreased with doses greater than 0.156 microgram/kg. The postprandial responses of IRI was also significantly suppressed with the same doses. On the other hand, the basal pancreatic exocrine secretion was significantly suppressed with doses greater than 0.625 microgram/kg. The postprandial pancreatic exocrine secretion was also significantly suppressed with doses greater than 0.625 microgram/kg. Those suppressions were dose-dependent. The postprandial CCK secretion was also significantly suppressed in dose-dependent manner with SMS201-995. The CCK suppression was significantly correlated with the suppression of pancreatic exocrine secretion. This clinical study under the setting of SAT demonstrated not only the direct inhibitory effect of somatostatin on both the islet and acinar cells but also, probably, the indirect inhibitory effect on the acinal cells via suppression of CCK release in humans.