Evaluation of the Effects of Cultured Bone Marrow Mesenchymal Stem Cell Infusion on Hepatocarcinogenesis in Hepatocarcinogenic Mice With Liver Cirrhosis.

OBJECTIVES: Liver transplantation remains the only curative therapy for decompensated liver cirrhosis. However, it has several limitations, and not all patients can receive liver transplants. Therefore, liver regenerative therapy without liver transplantation is considered necessary. In this study, we attempted minimally invasive liver regenerative therapy by peripheral vein infusion of bone marrow-derived mesenchymal stem cells (BMSCs) cultured from a small amount of autologous bone marrow fluid and evaluated the effects of BMSCs on hepatocarcinogenesis in a mouse model. METHODS: C57BL/6 male mice were injected intraperitoneally with N-nitrosodiethylamine once at 2 weeks of age, followed by carbon tetrachloride twice a week from 6 weeks of age onwards, to create a mouse model of highly oncogenic liver cirrhosis. From 10 weeks of age, mouse isogenic green fluorescent protein-positive BMSCs (1.0 × 106/body weight) were infused once every 2 weeks, for a total of 5 times, and the effects of frequent BMSC infusion on hepatocarcinogenesis were evaluated. RESULTS: In the histologic evaluation, no significant differences were observed between the controls and BMSC-administered mice in terms of incidence rate, number, or average size of foci and tumors. However, significant suppression of fibrosis and liver injury was confirmed in the group that received BMSC infusions. DISCUSSION: Considering that BMSC infusion did not promote carcinogenesis, even in the state of highly oncogenic liver cirrhosis, autologous BMSC infusion might be a safe and effective therapy for human decompensated liver cirrhosis.

[Endoscopic diagnosis of early cancer in the esophagogastric junctional region].

The endoscopic diagnosis of early esophageal and gastric cancers located within 2 cm above and below the esophagogastric junction (EGJ) is discussed. We reviewed 25 cases (10 mucosal cancers and 15 submucosal cancers). Histologically, early cancers frequently appeared as type IIc lesions (16/25: 64%). There was no relationship between tumor size and the depth of invasion of cancer lesions, and most of the lesions were well or moderately differentiated carcinomas. Endoscopically, homogenous redness with a thin white coating, some granular appearance, and easy bleeding were very important factors for the diagnosis of early gastric cancer. For superficial esophageal cancer, differential diagnosis from reflux esophagitis is correctly performed with the endoscopic dye (lugol)-staining method and biopsy. In order not to overlook early cancer at the EGJ, this area should be observed with sufficient air inflation by the U-turn or J-turn method using a frontal-view panendoscope.

Rational lymphadenectomy for early gastric cancer with submucosal invasion: a clinicopathological study.

Among all the patients who underwent gastrectomy for primary solitary gastric cancer at our department from 1979 to 1994, 228 patients had gastric cancer that invaded the submucosal layer. These cases were thus examined clinicopathologically, including the extent of submucosal invasion. No lymph node metastasis was found in any of the cancers measuring less than 2 cm in diameter. Macroscopic type I lesions or various combined types (IIa + IIc, IIc + IIa, IIc + III) were more likely to infiltrate deeply and were also associated with a high incidence (18%-25%) of lymph node metastasis. No lymph node metastasis or vascular invasion was found in any simple type IIa lesions. The incidence of lymph node metastasis was 3% in simple type IIc cancers measuring 3 cm or less. In addition, submucosal microinvasion (sm1) simple type IIc cancers showed no accompanying lymph node metastasis or vascular invasion. We thus conclude that a full-thickness partial resection of the stomach, such as a laparoscopic local resection, is applicable to cancers measuring 3 cm or less provided that they are either simple macroscopic type IIa or simple type IIc sm1 cancers.

Treatment of primary multiple early gastric cancer: from the viewpoint of clinicopathologic features.

The treatment of multiple early gastric cancer was investigated through the clinicopathologic assessment of 61 cases of primary multiple early gastric cancer (82 accessory lesions) treated by surgical resection over a 15-year period. These cases accounted for 11.7% of all cases of early gastric cancer resected during the same period. The 61 patients included 48 men (mean age 64 years) and 13 women (61 years). Of the 82 accessory lesions, 41 (50%) were located in the same region as the main lesion. The most frequent combination of macroscopic types of the main lesion and the accessory lesion was depressed type/depressed type (28 cases). The main lesion was of the well differentiated type in 39 (64%) of the 61 cases; the accessory lesion was also well differentiated in 37 of the 39 cases. Of the 82 accessory lesions, 29 (35%) had been overlooked preoperatively; most of them were located in the middle third of the stomach and included 17 depressed and 10 flat lesions, most of which measured no more than 1 cm. Cases of multiple early gastric cancer are characterized by the predominance of male patients of advanced age (> 60 years), a combination of the same macroscopic type of the main and accessory lesions, and well differentiated carcinoma. Lymph node metastasis and vascular invasion are equally or less frequent than in cases of solitary early gastric cancer. The postoperative crude survival rate in patients with multiple gastric cancer is similar to that in those with solitary gastric cancer. Therefore we believe that multiple early gastric cancer does not require extended operative procedures. Endoscopic treatment may be indicated if each lesion fits the criteria for treatment and careful follow-up is ensured.

Technical devices in jejunal pouch reconstruction following total gastrectomy, including postoperative results.

BACKGROUND/AIMS: Either straight Roux-en-Y anastomosis or jejunal interposition used to be adopted following total gastrectomy. However, dissatisfaction with regard to postoperative quality of life has prompted the development of new techniques. The purpose of this study is to describe and assess the authors' technical devices in jejunal pouch (J-pouch) reconstruction following total gastrectomy and the results of these operations. PATIENTS AND METHODS: A prospective study of 17 patients with malignant gastric disease (nine with J-pouch interposition, eight with J-pouch Roux-en-Y reconstruction) was performed. To facilitate the side-to-side anastomosis of the jejunal loop, the authors used an autosuture instrument. The anastomosis was then checked for hemostasis using a vaginoscope. RESULTS: An Endo GIA with a 60-mm long white cartridge (closed height of staples, 1.0 mm) is the instrument of choice to create the J-pouch. This autosuture instrument fires triple staggered staple lines, which minimizes bleeding from the anastomosed site and reduces operative time. No anastomotic leaks were associated with the autosuture instrument. The vaginoscope facilitates a direct observation of the staple lines internally and if necessary, enables secure hemostasis with sutures. Bowel motility was satisfactory for both surgical procedures, as measured by the percentage of radiopaque markers which were expelled from the pouch. There were no serious complications, and all patients have currently survived, a maximum of 5 years and 6 months after surgery, except for one patient who died from recurrent disease. CONCLUSION: The authors' procedures for J-pouch reconstruction are advantageous due to a favorable postoperative quality of life, with low complication rates.

Proximal gastrectomy and jejunal pouch interposition for the treatment of early cancer in the upper third of the stomach: surgical techniques and evaluation of postoperative function.

BACKGROUND: Limited surgery for the treatment of early gastric cancer located in the upper third of the stomach should be based on a well-balanced reduction in the extent of lymph node dissection and gastric resection while assuring a favorable quality of life and prognosis after operation. METHODS: We have used interposition of a double jejunal pouch between the esophagus and the remnant stomach after performing proximal gastrectomy. To assure anastomosis and hemostasis during this operation, we currently use a surgical stapler with a vaginoscope and our new edge clamps. This method has been used in 12 patients to date. RESULTS: On histopathologic examination the 12 cases comprised 11 early cancers (seven mucosal and four submucosal cancers) and one subserosal cancer. There was no evidence of lymph node metastasis of postoperative complications such as anastomotic leakages or hemorrhage, demonstrating the low-risk nature of this procedure. CONCLUSIONS: The evaluation of postoperative quality of life, in terms of clinical signs and symptoms and dietary status, yielded favorable results. Thus our method has the important advantage of allowing good organ preservation.

Endoscopic treatment of early oesophageal or gastric cancer.

BACKGROUND AND AIMS: Endoscopic treatment has become increasingly popular in recent years as an alternative to surgical treatment with the hope of offering superior quality of life (QOL) for the patient. The results of endoscopic treatment of mucosal lesions of mostly early oesophageal or gastric cancer performed in 145 patients (155 lesions) over the past eight years were reviewed from the standpoint of QOL. RESULTS: In 56 patients who underwent radical resection of the oesophageal mucosa, no serious complications and symptoms occurred, with epithelialisation completed within about a month. Patients also showed good results regarding dietary intake and performance status (PS), and all are currently alive without any sign of recurrence. One time fractionated endoscopic resection was carried out in about 40% of the 57 patients who underwent gastric mucosal resection. In these 57 patients, an artificial ulcer measuring 3 cm or more was formed, resulting in a favourable outcome after healing. An overwhelming proportion of these subjects had no symptoms and good PS after the treatment. CONCLUSIONS: The introduction of this method, endoscopic mucosal resection using a cap fitted panendoscope, is expected to permit additional indications for endoscopic treatment. Endoscopic Nd-YAG laser irradiation was applied mainly to early gastric cancer lesions (32 patients), usually for relative indications for endoscopic treatment. This procedure is safe and advantageous in that it requires no hospitalisation, permits fractionated irradiation, and secures good QOL.

A new method of endoscopic mucosal resection of neoplastic lesions in the stomach: its technical features and results.

BACKGROUND/AIMS: In gastric cancer, endoscopic treatment can be expected to provide an absolute cure only if the lesion is mucosal and not accompanied by metastatic lymph nodes. To further evaluate such possibly curable lesions, we retrospectively reviewed 208 cases of early gastric cancer surgically resected over the past 20 years. METHODOLOGY: Our new method of endoscopic mucosal resection using a cap-fitted panendoscope, which is called EMRC, has been employed in the treatment of 73 gastric neoplastic lesions. RESULTS: It was found that curable lesions would, as the primary condition, be histologically well-differentiated carcinomas and measure 2 cm or less of the elevated type and less than 1 cm of the depressed type. The lesions were consequently identified as 49 early cancers (46 mucosal, 3 submucosal), 23 adenomas and 1 carcinoid. Although resection was completed in a single session of EMRC treatment in all cases, approximately 40% of them required fractionated resection, leaving an ulcer measuring 3 cm or more in approximately 30%. Bleeding or muscle resection occurred in 7 patients, in whom conservative treatment was effective. No recurrence has been found in any of the 73 lesions, demonstrating a favorable outcome. CONCLUSIONS: This method is advantageous in that it is simple and relatively easily applied at almost any location within the stomach. In addition, the size of the specimen obtained by en bloc resection is approximately 2 cm. The method is thus fairly likely to come into widespread use.

General pharmacological properties of the human corticotropin-releasing hormone corticorelin (human).

General pharmacological effects of the human corticotropin-releasing hormone, corticorelin (human) (CAS 86784-80-7), on the central nervous system, somatic nervous system, autonomic nervous system and smooth muscle, respiratory and circulatory system, digestive system and miscellaneous organs were investigated. 1. The central nervous system: Corticorelin (human) had little effect on hexobarbital-induced sleeping-time, maximal electroshock-induced convulsion, acetic acid-induced writhing, rota-rod performance. Corticorelin (human) at doses of more than 10 micrograms/kg i.v. induced flush of skin and pilo-erection, at doses of more than 30 micrograms/kg i.v. decreased body temperature, delayed expression of perphenazine-induced catalepsy and indicated hunched posture, and at the dose of 100 micrograms/kg i.v. induced the rise of awake-level and decrease of the total power of EEG, and decreased the spontaneous motor activity. 2. The somatic nervous system: Corticorelin (human) did not cause muscle relaxation in mice and had little effect on neuromuscular transmission in rats. No local anesthetic activity of corticorelin (human) was exhibited through inhibition of the corneal reflex in guinea pigs. 3. The autonomic nervous system and smooth muscle: Corticorelin (human) had no effect on the contraction of isolated ileum of guinea pigs induced by histamine and acetylcholine, and on the contraction of isolated trachea of guinea pigs induced by histamine, and the pupil diameter of rabbits. Corticorelin (human) at doses more than 30 micrograms/kg i.v. decreased spontaneous motility and contractile force of uterus of non-pregnant rabbits. 4. The respiratory and circulatory system: Corticorelin (human) had no effect on the contraction of isolated aorta of rats induced by norepinephrine. Corticorelin (human) at doses of more than 3 micrograms/kg i.v. decreased the blood pressure, increased heart rates and slightly increased the number of respiration in dogs. However, corticorelin (human) had no effect on ECG and femoral blood flow in dogs. 5. The digestive system: Corticorelin (human) at doses of more than 0.3 microgram/kg i.v. increased duodenal motility and contractile force, at doses of more than 1 microgram/kg i.v. increased colonic contractile force transiently and increased antral motility. Corticorelin (human) at doses of more than 3 micrograms/kg i.v. caused diarrhea and at doses of more than 30 micrograms/kg i.v. inhibited small intestinal propulsion in mice. Corticorelin (human) at dose of 100 micrograms/kg i.v. showed an inhibition of the gastric juice secretion and decreased the excretion of Na+, Cl- and H+ in rats. Corticorelin (human) produced slight gastric damages only at the highest dose of 100 micrograms/kg i.v.(ABSTRACT TRUNCATED AT 400 WORDS)