Takeharu Hisatsugu

Prevention of recurrent bleeding from gastric ulcer with a nonbleeding visible vessel by endoscopic injection of absolute ethanol : a prospective, controlled trial

We performed a prospective, randomized trial to assess the efficacy of endoscopic injection therapy with absolute ethanol in preventing recurrent bleeding in patients with nonbleeding visible vessels in gastric ulcers. During the period of 1990 to 1993, 62 patients who bled were found to have gastric ulcers with nonbleeding visible vessels; all of them were enrolled for this trial. The 62 patients were randomly divided into two groups, which were comparable at entry. In group I (33 patients), we performed endoscopic injection therapy with absolute ethanol. In group II (29 patients), we sprayed the ulcers with 0.1% epinephrine and thrombin. Endoscopic injection therapy with ethanol was performed at the second endoscopy in the patients in both groups who had recurrent bleeding. Among the 33 patients in group I, 4 patients (12.1%) rebled after the initial ethanol injection therapy, whereas 10 of 29 patients (34.5%) rebled in the control group (p < .05). No patients in group I required surgical intervention, and ultimate hemostasis was achieved in all 33 group I patients (100%), indicating that endoscopic ethanol injection therapy achieves ultimate hemostasis and prevents recurrent bleeding in patients with gastric ulcers and nonbleeding visible vessels.

Effect of granulocyte colony-stimulating factor (G-CSF) on chemotherapy-induced oral mucositis

In this study, the ability of granulocyte colony-stimulating factor (G-CSF) to treat or prevent chemotherapy-induced oral mucositis in patients with advanced breast cancer was evaluated. A total of 14 patients who received intra-arterial (i.a.) adriamycin (ADM) preoperatively were divided into two groups according to whether or not G-CSF was given. Thus, group A (n=7) was given G-CSF and group B (n=7) was not. G-CSF therapy reduced both the incidence and duration of ADM-induced oral mucositis, and a positive correlation was also seen between the incidence of mucositis and ADM-induced leukopenia (<2,000/mm3). Group A was further divided into two subgroups according to whether G-CSF was given after or before the leukopenia had dropped below 2,000/mm3: group A-1 (n=3) and group A-2 (n=4), respectively. ADM-induced mucositis was observed in two of the three patients in group A-1, but in none of the four patients in group A-2. These results strongly support the idea that G-CSF can effectively treat and prevent ADM-induced oral mucositis.

Metastatic carcinoma of the gallbladder from renal cancer presenting as intraluminal polypoid mass

SummaryWe report a rare case of secondary involvement of the gallbladder by metastatic renal cell carcinoma. A 71-year-old man was diagnosed as having a polypoid mass within the gallbladder when he underwent right nephrectomy for a renal cell carcinoma. A preoperative diagnosis of simultaneous carcinoma of the gallbladder was made, and extended cholecystectomy with regional lymphadenectomy was performed five months after the initial operation.Postoperative histological examination of the polypoid mass within the gallbladder and a pancreatic mass excised during the second surgery revealed these resected tumors to be identical to the clear cell type of renal cell carcinoma. We feel that this case presents synchronous involvement of the gallbladder and pancreas by metastatic renal cell carcinoma of the right kidney.

A case of blue rubber bleb nevus syndrome with familial onset

SummaryWe experienced a case of blue rubber bleb nevus syndrome with familial onset. The patient was a 32-year-old male with a gallstone and many bluish rubber bleb-like hemangiomas on the skin. He suffered from repeated rectal bleeding and underwent a sigmoidectomy at age 17. Gastrointestinal hemangiomas were recognized in the esophagus, stomach, ileum and colon. An angiogram revealed multiple small poolings in the liver, suggesting the presence of hemangiomas. During the cholecystectomy, surgeons noted the presence of hemangiomas on the surface of the liver, serosa of the small intestine and retroperitoneum.Out of 73 blood relatives, 24 also had bluish skin hemangiomas, suggesting them to be inherited by an autosomal dominant trait.More than sixty cases of this syndrome had been reported in the world, eight of which had family histories of skin lesions. However, in only three cases, including our own, was the presence of skin and gastrointestinal hemangiomas recognized.Because the clinical indications for diagnosis of blue rubber bleb nevus syndrome consist of minimal to massive bleeding from the gastrointestinal tract, the possibility that this syndrome is present should be considered when diagnosing a bleeding patient with multiple bluish rubber bleb-like skin lesions, in addition to taking a detailed family history.

Medical dissolution of gallstones : clinical experience of d-limonene as a simple, safe, and effective solvent

Retained gallstones in the bile ducts account for 60–70% of all the cases of postchole-cystectomy syndromes. A solventd-limonene preparation was injected directly to the biliary system of 200 patients to dissolve or disintegrate the retained gallstones. The outcomes were: retained stones completely disappeared in 96 cases (48%); partial dissolution in 29 (14.5%); chelating agent was also used with partial dissolution in 16 (8%); ineffective in 59 (24.5%). To make this method more effective, several guidelines should be observed including anin vitro trial dissolution test. Cautious observation for possible side effects and frequent hepatic and pancreatic function tests during the treatment with this preparation also should be performed.

An unusual presentation of spontaneous pneumoperitoneum secondary to the rupture of a gas-containing pyogenic liver abscess: Report of a case

We describe a rare case of spontaneous pneumoperitoneum secondary to the rupture of a gas-containing pyogenic liver abscess in a 59-year-old man. The patient was diagnosed as having a hollow viscus perforation based on a sudden onset of acute abdominal pain along with radiological evidence of bilateral subphrenic feee air (pneumoperitoneum), and underwent an emergency laparotomy. Contrary to expectations, the surgery revealed no perforations of the hollow viscus, but instead a ruptured liver abscess at the dome of the right hepatic lobe was identified associated with suppurative peritonitis. To the best of our knowledge, such a case of spontaneous pneumoperitoneum secondary to the rupture of a gas-containing liver abscess is extremely rare.

Induction of tumor growth inhibitory factor (TGIF) in human mononuclear cells by OK-432, a streptococcal preparation

SummaryA tumor growth inhibitory factor (TGIF) was induced in the culture supernatant from mixed culture of human peripheral blood mononuclear cells (PBMC) and a streptococcal preparation, OK-432, in vitro. The activity generated in the supernatant increased in a time-dependent fashion and first appeared 6 h after the initiation of culture, reaching its maximum around 48 h. The TGIF was cytostatic against seven of ten human tumor targets, but not against three murine tumor targets. Tumor cell growth was inhibited by a transient contact, i.e., 1 h, with TGIF. The TGIF was produced by lymphocytes but not by monocytes, because the activity was usually enhanced by elimination of plastic-adherent cells from the original PBMC fraction. The TGIF was relatively stable against heating at 56° C for 30 min, but the activity was totally destroyed after heating at 70° C for 5 min. The molecular weight of TGIF was estimated to be about 43×103 daltons by gel filtration. No interferon (IFN) activity was detected in the TGIF-positive fractions obtained by gel filtration, and the TGIF-positive fractions did not inhibit the growth of tumor necrosis factor (TNF)-sensitive mouse L929 cells. The TGIF activity was not significantly affected in neutralizing tests using specific antibodies against human IFN and TNF. The OK-432 was administered i.p. for management of cancer patients with malignant ascites. Ascites-derived mononuclear cells (ASMC) were obtained before and 3 to 5 days after OK-432 injection. The ASMC obtained after the injection produced TGIF in vitro in the absence of OK-432; the preinjection ASMC showed no such production. A positive correlation was found between TGIF-producing activity by ASMC and the effect of OK-432 injection on ascites volume. These results indicate that TGIF is induced in mononuclear cells by OK-432 not only in vitro but also in vivo and plays an important role in inhibition of tumor growth in cancer patients.

Xanthogranulomatous Cholecystitis : Cell Composition and a Possible Pathogenetic Role of Cell-mediated Immunity

Summary Thirty-three cases o f xanthogranulomatous cholecystitis (XGC) exhibiting the typical morphologic features were studied by light and electron microscopy and immunohistochemical techniques. Incidence of XGC was 4.2% of the surgically resected gallbladder diseases. Histologically, the granulomatous lesion of XGC principally consisted of accumulations of foam cells and lymphocytes. Variable numbers of multinucleated giant cells, granulocytes and fibroblastic cells were also noted. With respect to the origin of foam cells, it was considered that the vast majority of foam cells were derived from monocyteslmacrophages because they were invariably positive for KP1, HAM56, CD 11b and CD68. Interspersed among macrophage foam cells, many T lymphocytes were identified. The subtyping of T cells indicated a heterogenous population composed of both CD4+ and CD8+ lymphocytes typically in a ratio of 1:2. Macrophages and T lymphocytes demonstrated a marked expression o f HLA-DR antigen. Electron microscopic and immunohistochemical double-staining observation demonstrated intimate apposition of T lymphocytes to macrophages or macrophage foam cells. The results indicate that XGC is a granulomatous disorder characterized by accumulations of macrophage foam cells and T cells. Delayed type hypersensitivity reaction of cell-mediated immunity may be implicated in the pathogenesis o f XGC.

Tumoricidal effect of human PBMC following stimulation with OK-432 and its application for locoregional immunotherapy in head and neck cancer patients.

Both cell-mediated and cytokine-mediated antitumor activities were induced in peripheral blood mononuclear cells (PBMC) in short-term culture with streptococcal preparation, OK-432. Kinetic analysis of OK-432-activated killer activity (OKAK) showed that it reached a plateau level much faster (by 48 h of culture) than that detected in PBMC stimulated with recombinant interleukin 2 (rIL-2) (lymphokine-activated killer: LAK). We also found that the tumor growth inhibitory factor (TGIF) activity was produced in the culture supernatant (CSN) of the OK-432-activated PBMC (OK-MC) and the activity synchronously increased with augmentation of OKAK activity. The TGIF activity was rarely found in the CSN of rIL-2-stimulated PBMC. The TGIF activity detected in CSN of OK-MC was further characterized as derived from a cytokine different from interferon gamma (IFN gamma), tumor necrosis factor (TNF), or lymphotoxin (LT) by a neutralization test using monoclonal antibodies to these cytokines. These 48-h-cultured-OK-MC were adoptively transferred (adoptive immunotherapy: AIT) into 19 head and neck cancer patients either alone or in combination with chemotherapy and/or radiation therapy, and their therapeutic effects were examined. AIT was performed by intra-arterial or intratumoral administration of OK-MC. There were no significant side effects observed in this treatment. In these patients, approximately 1-10 x 10(7) cells were transferred into the tumor burden. Of the 19 patients, 17 had primary cancer, and in 6 (6/17;35%) of them complete remission (CR) of the tumor was obtained. Partial remission (PR) was attained in 9 of the 17 patients (9/17; 53%), giving the overall response rate of 88%.(ABSTRACT TRUNCATED AT 250 WORDS)

Increased proliferation of a human breast carcinoma cell line by recombinant interleukin-2

Two adenocarcinoma cell lines, Breast M25-SF and Breast M, were established from tumor tissue resected surgically from a patient with breast cancer. One, Breast M25-SF, expresses interleukin-2 receptor (IL-2R) on the cell surface and the other, Breast M, does not. The effects of recombinant inteleukin-2 (rIL-2) on the proliferation of these cell lines were investigated. The growth of Breast M25-SF was significantly promoted by rIL-2 ranging from 1,25 U/ml to 640 U/ml. Anti-CD25 (Tac) antibody, significantly blocked the growth enhancement of Breast M25-SF by rIL-2. Breast M, however, did not respond to rIL-2. To confirm more directly the promotion of Breast M25-SF growth by rIL-2, cloning of IL-2 responders from parent Breast M25-SF cells was carried out by limiting dilution without feeder cells in 96-well microplates. No colony formation was found in 24 wells without rIL-2. Eleven, 13 and 6 clones were established from groups of 24 wells containing rIL-2 at 200, 20 and 2 U/ml respectively. All of the clones expressed IL-2R and respond to rIL-2. By using a sensitive polymerase chain reaction technique, we demonstrated that Breast M25-SF but not Breast M expressed IL-2 mRNA, and IL-2 secretion from Breast M25-SF but not Breast M was also confirmed by radioimmunoassay. These findings suggest a role for IL-2 in autocrine support of Breast M25-SF growth. IL-2 may play an important role in the growth control of breast carcinoma cells.