Kouhei Akazawa

Multivariate analysis of the histopathologic prognostic factors of cervical cancer in patients undergoing radical hysterectomy

Three hundred forty‐five patients with invasive carcinoma of the uterine cervix, Stages Ib (211 patients) and II I (134 patients), underwent radical hysterectomy and pelvic lymphadenectomy. The influence of histologic factors including histologic subtype, maximum depth of cervical stromal invasion, degree of stromal invasion, longitudinal tumor diameter, lymph‐vascular space invasion, corpus invasion, parametrial invasion, vaginal invasion, and pelvic lymph node (PLN) metastases on survival were examined by multivariate analysis. Univariate analysis revealed that all the variables except corpus invasion and vaginal invasion were significant in survival (P < 0,05). Among these variables, however, PLN metastases, histologic subtype, and longitudinal tumor diameter were identified as independent and significant prognostic factors by multivariate analysis using Cox regression models. The prognostic index (PI), defined by the model (an indicator of the patients place in the prognostic spectrum), was able to divide the patients into three prognostic groups. The key factors in the definition of these groups were (1) squamous cell carcinoma, small tumor diameter, and no PLN metastases for the good prognostic group and (2) PLN metastasis in two or more node groups, adenocarcinoma with one positive PLN group, or squamous cell carcinoma with one PLN group and large diameter for the poor prognostic group. These prognostic findings could predict the prognosis more precisely than that of clinical staging.

Estimation of risk of major complications after hepatic resection

To identify the risk factors predicting major postoperative complications from among preoperative and intraoperative variables, an extensive retrospective analysis of 209 patients who underwent hepatic resections was performed using multivariate logistic regression. The major complications were defined as liver failure, intractable ascites and pleural effusion, intraperitoneal infection, intra-abdominal hemorrhage requiring reoperation, major bile leakage, and gastrointestinal tract bleeding. First, detailed pre- and intraoperative data including medical history, laboratory data, portion and extent of hepatectomy, operative time, and amount of blood loss were univariately analyzed. Next, any significant variables were multivariately analyzed using the logistic regression method. Diabetes, increased intraoperative blood loss, resection of segment 8, and an increased serum blood urea nitrogen level were independent and significant variables predicting major postoperative complications. A higher level of serum cholesterol and a procedure involving a portion of left lateral segment were found to decrease the risk. Both more careful operative procedures and intensive management of DM and renal dysfunction in the perioperative period could result in a better quality of life after hepatic resection.

Primary gastric lymphoma. A clinicopathologic study of 233 cases with special reference to evaluation with the MIB-1 index

Background. Few articles have analyzed the prognostic data from a large series of primary gastric lymphoma classified according to the concept of mucosa‐associated lymphoid tissue (MALT).

Inverse correlation between the expression of bcl-2 and p53 proteins in primary gastric lymphoma

The immunohistochemical expression of bcl-2 and p53 proteins was evaluated in formalin-fixed, paraffin-embedded surgical specimens from 212 patients with primary gastric lymphoma. bcl-2 protein was found to be expressed in 145 specimens (68%). Among the 179 specimens with B-cell lymphoma of mucosa-associated lymphoid tissue (MALT), bcl-2 positivity decreased significantly as the histological grade advanced; bcl-2 was expressed in 93% of low-grade tumors, 88% of mixed-grade (low-grade with a focal high-grade component) tumors, and 44% of high-grade tumors (Cochrans linear trend test; P<.001). p53 protein expression was detected in 43 of 212 cases (20%). Among the B-cell MALT lymphomas, p53 positivity increased significantly as the histological grade advanced; p53 was expressed in 6% of low-grade tumors, 12% of mixed-grade tumors, and 31% of high-grade tumors (Cochrans linear trend test; P<.001). An inverse correlation was observed between the expression of bcl-2 and p53 in all 212 lymphomas (gamma = -0.531; P<.05) as well as in all 179 B-cell MALT lymphomas (gamma = -0.671; P<.01). Although the bcl-2 expression did not correlate with the patient survival, the p53 positive cases showed a significantly poorer prognosis compared with the p53 negative cases (log-rank test; P<.05). These results suggest that the expression of bcl-2 and p53 may, therefore, be associated with the transition from low-grade to high-grade tumors in primary gastric lymphoma.

Prognostic factors of vision in patients with Behcet disease

BACKGROUND Behçet disease is a chronic, recurrent, inflammatory disorder characterized by the triad of oral and genital ulcers and ocular lesions. The etiology is unknown. Although many of these patients become blind, some have good vision all their life. METHODS To attain more accurate data on the prognosis of these patients, the authors studied 52 Japanese patients (101 eyes) seen at Kyushu University Hospital between 1980 and 1990. At the first visit, patients ranged in age from 21 to 61 years; at onset, they ranged in age from 17 to 55 years; and the disease duration at first visit was from 0 to 22 years. Thirty-five of the 101 eyes had a visual loss of more than five lines or the patients became blind. The authors divided the subjects into two groups--favorable group and unfavorable group. If an eye had more than five lines of visual loss or the patient became blind 3 years after the first visit, it was placed in the unfavorable group, and if not, it was classed in the favorable group. Thirty-two factors determined from clinical records were used to select statistically significant risk factors for visual loss, using univariate analysis and multivariate logistic regression analysis. RESULTS Univariate analysis showed the following four factors that were significantly different between favorable and unfavorable groups: sex, disease interval, other complications, and skin lesions (first year). Multivariate analysis showed that the following seven factors had mutually independent contributions to visual loss: skin lesions; arthritis; posterior attacks; other complications (experienced), including gastrointestinal, vascular, and central nervous system lesions; female sex; disease interval; and anterior attacks. The first four factors have effects of losing vision, whereas the others are related to vision retention. CONCLUSION The authors find that skin lesions, arthritis, posterior attacks, and other complications are linked to loss of vision, whereas female sex, disease interval, and anterior attacks are related to retention of vision.

Umbilical vein endothelial cells are an important source of c-kit and stem cell factor which regulate the proliferation of haemopoietic progenitor cells.

The expression and production of c‐kit and its ligand, stem cell factor (SCF), in cord blood and neonates were studied. Serum SCF levels were significantly higher in cord blood, neonates aged 1–30 d, and in 4‐month‐old infants than in the maternal serum (P < 0.01). SCF levels decreased in children from 7 months to 15 years of age (P < 0.01). The serum soluble c‐kit levels were significantly higher in cord (P < 0.01) and neonatal blood (P < 0.05) than in the maternal blood. SCF and c‐kit levels in placental tissue homogenates and the culture media of decidual cells and trophoblasts were low. To determine the sites of high SCF and c‐kit production in cord blood and in early neonates, SCF and c‐kit mRNA expression was analysed in various tissues by polymerase chain reaction. High SCF mRNA expression was observed in human umbilical vein endothelial cells (HUVEC). Moderate c‐kit mRNA expression was detected in HUVEC, the bone marrow, and cord blood. These findings suggest that endothelial cells mainly produce the SCF in cord blood and in early neonates. To confirm the role of endothelial cells in haemopoiesis, colony‐forming assays were performed in the presence of HUVEC culture media, which induced the formation of high numbers of granulocyte and erythroid colonies in cord blood. IL‐3, IL‐6 and SCF levels were elevated in the media. Our findings suggest that endothelial cells have an important role in the maintenance and proliferation of progenitor cells in neonatal blood via the interaction of c‐kit and SCF with other factors. The ex vivo expansion of cord progenitor cells in the presence of endothelial cells needs to be investigated further.

Power of logrank test and Cox regression model in clinical trials with heterogeneous samples

This paper evaluates the loss of power of the simple and stratified logrank tests due to heterogeneity of patients in clinical trials and proposes a flexible and efficient method of estimating treatment effects adjusting for prognostic factors. The results of the paper are based on the analyses of survival data from a large clinical trial which includes more than 6000 cancer patients. Major findings from the simulation study on power are: (i) for a heterogeneous sample, such as advanced cancer patients, a simple logrank test can yield misleading results and should not be used; (ii) the stratified logrank test may suffer some power loss when many prognostic factors need to be considered and the number of patients within stratum is small. To address the problems due to heterogeneity, the Cox regression method with a special hazard model is recommended. We illustrate the method using data from a gastric cancer clinical trial.

Risk factors for low birthweight in Japanese infants

The purpose of our study was to identify risk factors for low birthweight (LBW; birthweight < 2500 g) in Japanese infants. The data was collected from questionnaires completed by the parents of 23 132 infants who underwent a standardized well baby check‐up for 1‐month‐old infants, conducted by the Fukuoka City Medical Association from 1987 to 1995. The following eight factors and their second‐order interaction terms were examined as potential risk factors for LBW: maternal age at delivery, history of live‐born LBW infant, history of abortion in previous pregnancies, maternal smoking, coffee and alcohol consumption during pregnancy, prenatal training and live birth order. The results of multiple logistic regression analysis showed that the following three factors and one interaction term significantly contributed to LBW: history of live born LBW infant, maternal smoking, live birth order and the interaction between maternal smoking and live birth order. The smoker‐related risk for LBW was quite different in each of the three groups stratified by live birth order. Efforts should be made, for example, to increase the accessibility of early, high‐quality prenatal care for the high‐risk groups with previous LBW babies and to implement smoking intervention, ranging from specific medical procedures to broad‐scale public health and health‐related educational programs in schools.

Serum vascular endothelial growth factor: a new predictive indicator for the occurrence of coronary artery lesions in Kawasaki disease.

Abstract We investigated serum vascular endothelial growth factor (SVEGF) levels in Kawasaki disease and determined whether these levels had any association with the development of coronary artery lesions. We measured SVEGF levels in 66 patients with Kawasaki disease, 18 patients with active infections and 18 afebrile controls. SVEGF levels of patients in the acute phase of Kawasaki disease (0.0–2003.6 pg/ml, median 59.87 pg/ml) were significantly higher than those of patients with active infections (0.0–45.2 pg/ml, median 8.10 pg/ml; P < 0.05) or afebrile controls (0.0–49.8 pg/ml, median 7.75 pg/ml; P < 0.05) and decreased to undetectable or low levels in the recovery phase (n=31, acute phase: 0.0–2003.6 pg/ml, median 62.50 pg/ml versus recovery phase: 0.0–146.5 pg/ml, median 26.90 pg/ml; P=0.0007) of the disease. There existed a positive correlation between SVEGF levels and serum C-reactive protein concentrations in the acute phase of Kawasaki disease (rs=0.347, P=0.0051). In addition, SVEGF level and duration of fever were found to be major risk factors for the occurrence of coronary artery lesions by univariate (P=0.012 and P=0.003, respectively) and multivariate (P=0.037, OR 6.16 and P=0.0059, OR 7.59, respectively) analyses. Conclusion Serum vascular endothelial growth factor level, in combination with persistence of fever, could be a powerful predictor for the development of coronary aneurysms.

Correlation between metastatic site, histological type, and serum tumor markers of gastric carcinoma

Gastric carcinoma is classified into intestinal type carcinoma (IC) and diffuse type carcinoma (DC). Intestinal type carcinoma usually tends to metastasize to the liver and DC to the peritoneal cavity. However, discrepant cases are sometimes seen: IC with peritoneal metastasis or DC with liver metastatic site with special reference to these discrepant cases. We also studied the serum tumor markers (carcinoembryonic antigen [CEA] and carbohydrate antigen [CA] 19-9). We studied 124 autopsied specimens of patients who died of gastric carcinoma. The primary tumors were classified as IC or DC. The discrepant cases included 19 DCs with liver metastasis and 19 ICs with peritoneal dissemination. Most discrepant cases focally had histological features in the primary tumor consistent with our main supposition. On the other hand, discrepant foci were seen only very rarely in the primary tumor of cases with the corresponding usual metastatic site. The serum CEA levels of specimens from cases with liver metastases were higher than those without liver metastases. The serum CA 19-9 levels showed no significant correlation with the metastatic site of the carcinoma. In conclusion, in gastric carcinoma (1) the metastatic site was correlated with histological type (2) even in cases showing a discrepant metastatic site, focal areas of the histological type consistent with our main findings could be found in the primary tumor, and (3) serum CEA levels correlated with liver metastasis.