Growth pattern and expressions of cell cycle regulator proteins p53 and p21WAF1/CIP1 in early gastric carcinoma.

BACKGROUND: The growth pattern of early gastric carcinoma, as based on a volumetric analysis, reflects the biologic characteristics of a tumor. The penetrating growth (Pen) type tumor has an unfavorable prognosis, compared with the case of a superficially spreading (Super) type. The wild-type of the p53 protein plays an important role in cell growth regulation and apoptosis. The p21 protein, which is encoded by the WAF1/CIP1 gene, is a downstream target effector of wild-type p53 protein, and these proteins act as tumor suppressors in a negative cell-cycle regulation. METHODS: In 133 Japanese patients with early gastric carcinoma with submucosal invasion, expressions of p53 and p21 proteins were studied immunohistochemically, and the relation between growth pattern and expressions was analyzed. RESULTS: Early gastric carcinomas were grouped into the superficially spreading (Super) type 40 (30.1%) cases, expansively penetrating growth (Pen-A) type 28 (21.1%), infiltratively penetrating growth (Pen-B) type 20 (15.0%), small mucosal type 35 (26.3%), and mixed type 10 (7.5%). The Pen-A type tumors were characterized by the highest incidence of p53 expression and loss of p21 expression, and the rate of p53-positive and/or p21-negative cases was 71.4%. There were significant differences in the incidence of the p53 expression (50.0% vs.25.0%), the loss of p21 expression (53.6% vs. 27.5%), and the 5-year survival rate (83.2 %vs. 97.2%) between the Pen-A type and the Super type. CONCLUSIONS: Thus, deregulation of the cell cycle by p53 and p21 in this study was shown to play an important role in progression of Pen-A type early gastric carcinoma.     

Pilot study of combination chemotherapy of S-1, a novel oral DPD inhibitor, and interferon-alpha for advanced hepatocellular carcinoma with extrahepatic metastasis

BACKGROUND: To the authors' knowledge, there is no effective therapy for extrahepatic metastasis of hepatocellular carcinoma (HCC). In a pilot study, the results of combination therapy of S-1, a novel oral dehydropyrimidine dehydrogenase (DPD) inhibitor, and interferon-alpha (IFN-alpha) are reported for HCC patients with extrahepatic metastasis. METHODS: Twelve patients with extrahepatic metastasis of HCC were enrolled in the pilot study. S-1 was administered orally at a dose based on body surface area, twice daily after a meal, for 4 weeks. IFN-alpha was injected subcutaneously on Days 1, 3, and 5 of each week. One course consisted of consecutive administration for 28 days followed by 14 days rest. RESULTS: An objective response was observed in 3 (25%) of 12 patients. The overall 1-year survival rate was 61.7%. Grade 3 leukocytopenia was observed in 1 patient (8.3%). No severe toxicity or treatment-related deaths were observed. CONCLUSIONS: The combination therapy of S-1 and IFN-alpha appears to be highly efficacious, with low toxicity in patients with extrahepatic metastases of HCC. The combination chemotherapy of oral S-1 and subcutaneous IFN-alpha is a potentially promising treatment strategy for advanced HCC with extrahepatic metastasis.     

Defective mitogen-activated protein kinase (ERK2) signaling in gastric mucosa of portal hypertensive rats: potential therapeutic implications.

Portal hypertensive (PHT) gastropathy is a frequent, serious complication of liver cirrhosis. PHT gastric mucosa has numerous abnormalities such as reduced mucosal potential differences, reduced surface oxygenation, and increased susceptibility to injury caused by alcohol, aspirin, and other noxious factors. Because such mucosal injury is initially mediated by oxygen free radicals, and because mitogen-activated protein (MAP) kinase (ERK2) protects against cellular stress and induces cell proliferation, we postulated that oxidative stress-induced ERK2 activation is defective in PHT gastric mucosa. Here we show that in PHT gastric mucosa, ERK2 activation by oxidative stress is impaired. This impairment is mediated by overexpression of MAP kinase phosphatase-1 (MKP-1), which results from the underlying and continual oxidative state associated with portal hypertension, and is ameliorated by inhibiting MKP-1. Furthermore, we found that supplementing vitamin E, a free radical scavenger, reduces the oxidative state in PHT gastric mucosa, normalizes MKP-1 expression, and thereby reverses impairment of oxidative stress-induced ERK2 activation. Finally, we show that orally administered vitamin E completely reverses the increased susceptibility of PHT gastric mucosa to alcohol injury. Our findings point to a new molecular and mechanistic basis for PHT gastropathy and provide a new therapeutic modality for protection of PHT gastric mucosa.     

Features and outcome of neonatal leukemia in Japan: experience of the Japan infant leukemia study group

BACKGROUND: Neonatal leukemia characterized by early stem cell origin and extramedullary infiltration in the first 4 weeks of life is rare. We analyzed the features and outcome of neonatal leukemia in Japan to establish an appropriate treatment strategy for this rare disorder. PROCEDURE: Patients with infant leukemia registered and treated in the Japan Infant Leukemia Study between 1996 and 2001 were analyzed. RESULTS: Among 162 infant leukemia patients, 11 exhibited neonatal leukemia; frequencies for all infant leukemias were 6.9% (8/116) for acute lymphoblastic leukemia (ALL) and 7.3% (3/41) for acute myeloid leukemia (AML). Positive MLL gene rearrangement was observed in all eight patients with ALL; a single patient with AML displayed germline configuration. Acute monoblastic leukemia was apparent in all three patients with AML (M5a in the FAB classification). Most of the patients demonstrated hepatoplenomegaly and hyperleukocytosis at diagnosis. Cutaneous and central nervous system involvement were detected in half of the patients. Four patients (one with AML, and three with ALL) have survived following stem cell transplantation (SCT); however, growth impairment related to SCT was observed in these patients. CONCLUSIONS: These results suggest an improvement attributable to treatment of neonatal leukemia. International-based collaborative studies are necessary to investigate the biology of this condition and to establish appropriate therapeutic strategies.     

Asymptomatic atresia of the lobar bronchus of the lung: a case report.

A 64-year old woman presented with an asymptomatic occlusion of the intermediate bronchus associated with a peripheral mass occupying the entire middle and lower lobes. As malignancy was suspected, inferior bilobectomy was done. There was a complete atelectasis of both lobes, with massive parenchymal necrosis. Pathological examinations suggested a tuberculous granuloma in the bronchus and parenchyma although tuberculous bacilli were not found. This case was unusual as congenital anomaly, and was suspected as bronchial tuberculosis.     

Left ventricular contractility is reduced by hypercapnic acidosis and thoracolumbar epidural anesthesia in rabbits

PURPOSE: We have previously observed that sympathetic blockade by epidural anesthesia (EA) modifies the cardiovascular response to marked hypercapnic acidosis in dogs. Our objective was to determine whether the combination of marked hypercapnic acidosis and EA reduce left ventricular contractility. METHODS: We randomly assigned 22 Japanese white rabbits anesthetized with isoflurane (1.0%) to two groups according to the absence (control group, n= 11) or presence (EA group, n= 11) of thoracolumbar EA. After epidural injection (0.5 mL.kg(-1) of 0.9% saline in the control group or 1% mepivacaine in the EA group) and during subsequent hypercapnia (mean arterial CO2 tension 85 mmHg), we measured left ventricular pressure, left ventricular volume by using conductance catheter and plasma catecholamine concentrations. Left ventricular contractility was assessed by the slope of the linear approximation of the left ventricular end-systolic pressure-volume relationship, [i.e., end-systolic elastance (Ees)]. RESULTS: The combination of hypercapnic acidosis and thoracolumbar EA caused a 65% decrease in Ees (P <0.05). Hypercapnic acidosis alone caused a 16% decrease (P <0.05) and thoracolumbar EA alone caused a 49% decrease in Ees (P <0.05). In the EA group, epidural injection caused an 85% decrease in the epinephrine concentration (P <0.05) and a 39% decrease in the norepinephrine concentration (P <0.05), even during hypercapnic acidosis. However, in the control group, hypercapnic acidosis caused no change in the circulating epinephrine concentration but a 74% increase in the circulating norepinephrine concentration (P <0.05). CONCLUSION: Combined hypercapnic acidosis and EA markedly reduce left ventricular contractility in an additive fashion in rabbits receiving general anesthesia.     

Perioperative Hemodynamics in Patients Undergoing Partial Left Ventriculectomy

OBJECTIVES: Effects of partial left ventriculectomy (PLV) were studied by analyzing perioperative hemodynamics with measurements of left ventricular (LV) pressure-volume (PV) relationships and thermodilution catheter measurements in the pulmonary artery. METHODS: Between July and October 1996, 43 consecutive patients underwent PLV with and without mitral valvuloplasty with a thermodilution catheter and PV loop analysis immediately before and after surgery. Patients were 52+/-13 years and 67+/-13 kg, with reduced functional capacity (New York Heart Association 3.3+/-0.3) due to cardiomyopathy (24), ischemic disease (13), valvular disease (3), and Chagas' disease (3). RESULTS: PLV required cardiopulmonary bypass for 44+/-24 minutes, with the heart arrested in 10 patients for 26+/-22 minutes for coronary artery bypass grafting (8), aortic valve replacement (2), and autotransplantation (2). Two patients failed to come off bypass, six died in the hospital and 35 (35 [81.4%] of 43) were discharged. Changes in PV loops included decreased end-diastolic and end-systolic volume, resulting in no change in stroke volume. Pulmonary artery wedge pressure decreased despite elevated end-diastolic pressure. Ejection fraction, end-systolic elastance (E-max), afterload recruitable stroke work, and volume intercepts all improved and resulted in similar stroke work with less energy expenditure (less PV area), thus improving myocardial energetic efficiency. CONCLUSION: Results suggest that PLV improves systolic function but decreases diastolic compliance, which results in reduced net ventricular function immediately after surgery. Thus, immediate hemodynamic improvements appeared to derive from reduced severity in mitral regurgitation and perioperative load manipulation. Improved myocardial energetics may ameliorate LV function and improve the course of underlying myocardial disease.     

Clinicopathologic characteristics of esophageal squamous cell carcinoma in younger patients

Background. The aim of the current study was to find out the clinicopathologic characteristics of younger patients with squamous cell carcinoma of the esophagus.

Methods. A total of 259 patients with esophageal squamous cell carcinoma who had been treated by esophagectomy and reconstruction within 10 years between January 1990 and December 1999 were studied. Clinicopathologic characteristics were compared between 27 patients younger than 50 years and 232 patients 50 years and older.

Results. A significant difference was observed with regard to the size of the tumor (6.3 ± 3.8 cm in younger patients versus 5.0 ± 2.4 cm in older patients; p = 0.017). The proportion of patients with TNM stage III or IV in younger patients (59.3%, 16 of 27) was significantly higher than that in older patients (38.3%, 89 of 232; p = 0.020). Nevertheless, no significant difference in the 1-, 3-, and 5-year survival rates was observed between younger patients (77.2%, 54.7%, and 54.7%, respectively) and older patients (81.9%, 54.2%, and 48.8%, respectively).

Conclusions. Although the prognosis of younger patients with esophageal squamous cell carcinoma did not differ from that of older patients, esophageal squamous cell carcinoma in younger patients has more malignant potential and aggressive activity.     

Cancer in adolescents and young adults in Japan: epidemiology and cancer strategy

According to national cancer registry data in Japan, approximately 20,000 adolescents and young adults (AYAs, age 15–39 years) are newly diagnosed with cancer each year. Improvements in treatment and care for AYAs with cancer are included in the Phase Three Basic Plan to Promote Cancer Control Programs in Japan. This article reviews current cancer incidence and survival for AYAs with cancer in Japan using population-based cancer registry data. Mortality data through 2019 from the Vital Statistics of Japan are also described. Encouragingly, the 5-year survival probability for AYA cancers has continued to improve, in parallel with childhood cancers, and the mortality rate has decreased. There has been increasing attention to these vulnerable patients and improved partnerships and collaboration between adult and pediatric oncology; however, obstacles to the care of this population still exist at multiple levels. These obstacles relate to specific areas: research efforts and enrollment in clinical trials on AYA malignancies, AYA-specific psychosocial support such as education, financial support, and oncofertility care, and cancer care systems. It is important for Japanese oncologists, health care providers, and health policy makers to recognize that the AYA population remains vulnerable and still have unmet needs.