Surgical management of endocrine tumor of the pancreas in Japan

Endocrine tumor of the pancreas is potentially malignant. A multicenter analysis of these tumors was conducted to clarity the present status of their surgical management and the subsequent long-term surgical results. The Japan pancreatoduodenectomy (JPD) study group carried out the study; 368 patients were enrolled and variables related to tumor characteristics, surgery, and survival were retrospectively analyzed. There were 222 patients with functioning tumor and 143 patients with nonfunctioning tumor. Malignant tumor was found in 140 of 368 (38%) of the patients, and 63/140 (45%) of these patients had metastatic lesion; the most common site of the metastasis was liver 34/136 (25%), followed by regional lymph nodes 26/136 (19%). Pancreatic resection was performed in 91% of patients with nonfunctional tumor and in 83% of those with malignant tumor, and 73% of the pancreatic resections were done with lymph node dissection. The overall 5-year actuarial survival rate was 76% in patients with malignant tumor. The actuarial 5-year survival rate was 93% in the patients without metastasis and 83% in patients who received curative resection. Multivariate analysis showed that the presence or absence of synchronous metastasis was the sole significant prognostic factor. The results suggest that: (i) malignant endocrine tumor of the pancreas is a curable malignancy when pancreatic resection with lymph node dissection is adopted and (ii) that synchronous metastasis is the dominant prognostic factor. This study was carried out as a group project. The authors' institutions are as follows     

Temporal and spatial expression of transforming growth factor-β in the healing patellar ligament of the rat

We investigated the temporal and spatial expression of transforming growth factor-β in the healing patellar ligament of the rat by immunohistochemistry. The mid-portion of the medial half of the patellar ligament in 14-week-old male Wistar rats was cut transversely with a scalpel. On day 1 after ligament injury, diffuse staining for transforming growth factor-β was observed in the extracellular matrix filling the wound, and the staining in the adjacent ligament tissue was as weak as it was in the normal ligament. On day 3, the intensity of the diffuse extracellular staining decreased, and the staining was observed in correspondence with the cellular distribution in the wound site and in the adjacent uninjured ligament tissue. On day 7, the intense staining was widely distributed over the whole length of the ligament tissue. On day 28, the staining for transforming growth factor-β was still observed at the wound site and in the adjacent uninjured ligament tissue, where the staining was reduced in intensity but still stronger than it was in the normal ligament. On day 56, the expression of transforming growth factor-β was still detectable at the wound site: however, in the adjacent uninjured ligament tissue, it had almost subsided to the normal level. The results of the present study suggest that ligament healing may be accompanied by extensive changes in the expression of transforming growth factor-β over the whole length of ligament tissue.     

Specific Changes of Urinary Excretion of Cross-Linked N-Telopeptides of Type I Collagen in Pre- and Postmenopausal Women: Correlation with Other Markers of Bone Turnover

Urinary excretion of cross-linked N-telopeptide of type I collagen (NTx) has been reported to be a specific marker of bone resorption [18]. We assessed a new immunoassay for NTx as an indicator of changes in bone resorption caused by spontaneous menopause and compared cross-sectionally the levels of urinary NTx, hydroxylysylpyridinoline (HP), lysylpyridinoline (LP), hydroxyproline (OH-Pr), other serum biochemical indices, and lumbar spine and proximal femur bone mineral density (BMD). Eighty-one Japanese women aged 22–77 participated in this study; 36 were premenopausal and 45 were postmenopausal. Urinary HP, LP, and NTx stayed at low levels in the premenopausal period and rose 21%, 30%, and 67% in the postmenopausal period, respectively. The rise in LP and NTx was statistically significant (P < 0.01), suggesting that NTx is mostly released from bone matrix when bone resorption is accelerated. When premenopausal women were divided into two age groups and postmenopausal women were divided into two groups according to years since menopause (YSM) there were significant differences in LP and NTx between women <4 YSM and women aged <40 and those women aged 41+ (P < 0.01 and P < 0.05, respectively). A significant 110% increase in urinary NTx and a 48% increase in urinary LP were observed in postmenopausal women compared with age-matched premenopausal women aged 45–55. All biochemical markers other than serum PTH correlated significantly with each other (r = 0.243–0.858, P < 0.05–0.0001). Urinary NTx inversely correlated with lumbar spine BMD. When postmenopausal women were divided into three groups, the correlation between bone resorption and formation markers in women 0-1 YSM was greater than in women 2–10 YSM and in women 11 + YSM, indicating that resorption and formation are coupled at the early postmenopausal period. We conclude that urinary NTx is responsive to changes in bone metabolism caused by estrogen deficiency and may be a more sensitive and specific marker than HP, LP, or OH-Pr in the early postmenopausal years. Received: 15 February 1995 / Accepted: 18 October 1996     

Possible mechanism of ruthenium red antagonism of capsaicin-induced action in the isolated guinea pig ileum.

Ruthenium red (3-5 microM) antagonism of the inhibitory effect of capsaicin (1 microM) on the contractile response to mesenteric nerve stimulation in the presence of hexamethonium (50 microM) and guanethidine (2 microM) was reversed significantly by sialic acid (2 mM) or neuraminidase (0.1 U/ml). These results suggested that ruthenium red at low concentrations inhibits the capsaicin-induced desensitization of activated Ca2+ influx into sensory nerves at least in part by binding to sialic acid residues.     

Immunohistochemical characterization of cellular infiltrates in squamous cell carcinoma and Bowen's disease occurring in one patient.

We investigated populations of the infiltrating cells in Bowen's disease (BD) and squamous cell carcinoma (SCC), both of which arose in the same patient, using the Avidin-Biotin-peroxidase complex method with eight monoclonal antibodies. T lymphocytes were most predominant among infiltrating cells; NK cells, B cells, and monocytes were rarely seen in either BD or SCC. Analysis of subsets of the infiltrating T lymphocytes revealed that the number of suppressor/cytotoxic (s/c) T cells was twice that of helper/inducer (h/i) T cells in BD, while the number of s/c T cells was lower than that of h/i T cells in SCC. The immunohistochemical results in the present case differed from those of predominant infiltration of h/i T cells and of s/c T cells in three other reports of BD and SCC. These results suggest that the population of the cellular infiltrates may be modulated by the nature of tumors and by the immuno-competent state of the hosts.     

A sheep survived for 48 days with the biventricular bypass type total artificial heart

A biventricular bypass type total artificial heart (BVB-TAH) utilizing two pusher-plate pumps was developed and implanted in a sheep for 48 days with excellent results. A Hall effect sensor was utilized to operate each pump independently with a full stroke at variable rates (VR). With this system, the animal's hemodynamics was kept physiologically, and all metabolic parameters except hemoglobin and hematocrit returned to normal three weeks after implantation. However, signs of infection appeared on the forty-second day, and consequently the animal fell into a state of shock. Even at that time the BVB-TAH maintained circulation by increasing pumping rate automatically. On the forty-eighth day, the animal could not stand and suffered from anuria; the experiment was then terminated after 1,140 h pumping. At autopsy, there was an enlarged heart with an atrophic change, 1,900 ml of pleural effusion, and 3,100ml of ascites fluid. Blood culture taken on the forty-seventh day yielded Acinetobacter calcoaceticus. The BVB-TAH operated in an independent VR mode maintained entire circulation, and has a capability of substituting the native heart function in any situation.     

Myrocin C, a new diterpene antitumor antibiotic from Myrothecium verrucaria. I. Taxonomy of the producing strain, fermentation, isolation and biological properties

A new diterpene antitumor antibiotic, myrocin C, has been isolated from the culture filtrate of a soil fungus, Myrothecium verrucaria strain No. 55. The antibiotic was effective against Gram-positive bacteria, fungi and yeasts, and prolonged the life span of mice bearing Ehrlich ascites carcinoma.     

Ethylnitrosourea-induced apoptosis in primordial germ cells of the rat fetus.

Ethylnitrosourea (ENU) is a simple alkylating agent. It induces gene mutations in fetal primordial germ cells (PGCs), and a high incidence of congenital malformations is also found in the offspring of male mice treated with ENU at the embryonic stage. It is also reported that decreases in the fertility rate and weights of the testis and ovary were found in the offspring from dams treated with ENU. In this study, we analyzed the occurrence of apoptotic cell death and the expression of p53 protein which is thought to play an important role in the DNA damage-induced apoptosis after administration of ENU to pregnant rats on day 13 of gestation to obtain a clue for clarifying the toxic effect of ENU on PGCs. Apoptotic cells increased in PGCs in fetal gonads from 3 h after treatment. The number of apoptotic PGCs peaked at 6 h and gradually decreased towards 24 h after treatment. On the other hand, p53-positive PGCs increased from I h after treatment, prior to the induction of apoptosis. The number of p53-positive PGCs peaked at 3 h and returned to the control level at 24 h after treatment. These results suggest that ENU induces apoptosis in rat fetal PGCs immediately after its administration to dams and excess cell death by apoptosis may have a close relation to the later occurrence of decreases in the fertility rate and gonadal weight. Moreover, a possible involvement of p53 is suggested in the ENU-induced apoptosis in PGCs.