Effects of supplemental oxygen on urinary 8-hydroxy-2'-deoxyguanosine levels in extremely low birth weight infants.

As the effects of supplementary oxygen on urinary excretion of 8-hydroxy-2'-deoxyguanosine (8-OHdG) are poorly understood, urinary 8-OHdG levels (ng/mg creatinine) were determined longitudinally on the postnatal day (PND) 1, 3, and 30 in 16 neonates with birth weight < 1000 g. No supplementary oxygen was required in 9 neonates during the first 24 h of life. Urinary 8-OHdG level on PND 1 was inversely correlated with birth weight in these 9 neonates (P = 0.0323) and was higher in four with birth weight < 750 g than five with birth weight > 750 g (41.0 ± 6.9 vs. 5.6 ± 2.7, respectively, P = 0.0200). Median urinary 8-OHdG on PND 1 of these 9 neonates was significantly lower than that of 7 neonates with oxygen (9.3 vs. 60.2, respectively), although there were no significant differences in clinical background, such as birth weight, between the two groups. Five of the 9 did not require supplemental oxygen at all during the first 30 days of life. Median urinary 8-OHdG levels were consistently significantly lower in the 5 neonates than in 11 neonates with oxygen transiently or persistently (9.3 vs. 54.6, 19.1 vs. 61.4, and 28.3 vs. 145 on PND 1, 3, and 30, respectively), although there were no differences in clinical background, such as birth weight, between the two groups. Urinary 8-OHdG on PND 30 was significantly positively correlated with supplemental oxygen dose on PND 30 (P < 0.0001), but not with birth weight in the 16 neonates. These results suggest that higher supplemental oxygen tension caused higher urinary 8-OHdG in this population.

Radiographic findings of diaphragmatic hernia and hypoplastic lung.

OBJECTIVE: Congenital diaphragmatic hernia (CDH) has a poor prognosis, despite intensive management. The prognosis of CDH is correlated with hypoplastic lung, but it is difficult to measure the degree of hypoplasia. The aims of this study were, therefore, to examine the relationship between chest X-ray and prognosis, and to assess whether the radiographic findings were a good indicator of hypoplastic lungs in patients with CDH. STUDY DESIGN: Fifty neonates with CDH were classified radiographically into apex and hilar types. To assess the differences in clinical course between these two groups, gestational age, birth weight, prenatal diagnosis, survival rate, requirement of extracorporeal membrane oxygenation (ECMO) therapy and lung area on X-rays were analyzed. RESULTS: In all, 32 cases were of the apex type and 18 were hilar. The survival rate of the hilar group (33%) was significantly worse than that of the apex group (81%) (P<0.001). The hilar group required ECMO therapy more frequently than did the apex group. CONCLUSIONS: The present results show a significant correlation between survival rate and the findings of chest X-rays in CDH. Radiographic findings are thus a good clinical indicator of the prognosis of CDH in neonates.

Immature teratoma of gallbladder associated with gliomatosis peritonei, a case report.

The patient was a 9-month-old girl who presented with an abdominal mass. Computed tomography scan revealed that the huge heterogeneous mass with cystic, calcified, and solid components occupied the upper abdomen, and diagnosis of teratoma was made preoperatively. At the operation, a tumor arising from gallbladder and gliomatosis peritonei with intact ovaries were found. This is a rare case report of teratoma that originated in the gallbladder associated with gliomatosis peritonei.

The expression of cadherins in human neuroblastoma cell lines and clinical tumors.

Cadherins are Ca(2+)-dependent cell-cell adhesion molecules which play crucial roles in the cell-cell interactions during development, tumorigenesis and metastasis. The absence of N (neural)-cadherin is correlated with the onset of neural crest migration and its reappearance is correlated with the cessation of migration and precedes gangliogenesis. We investigated the expression of cadherins including N-cadherin in five cell lines and eleven clinical specimens of human neuroblastomas, which originated from neural crest cells. We found that three of the neuroblastoma cell lines and all the clinical specimens were positive for the expression of the N-cadherin protein. The other two neuroblastoma cell lines were negative for the expression suggesting they originated from migrating neural crest cells. All these cell lines and clinical samples expressed either cadherin-6, cadherin-11 or both, i.e. cadherins expressed on neural crest cells, supporting their neural crest origin.

Plasma fatty acids concentrations in postoperative patients with biliary atresia.

The concentrations of plasma fatty acids in postoperative patients with biliary atresia (BA) were measured to clarify whether they had essential fatty acid deficiency. Thirty-eight fasting blood samples from 14 postoperative patients with BA were studied. All of them had the hepatic portoenterostomy without any stoma. Samples were divided into three groups on the basis of liver function. The concentrations of fatty acids in the plasma fat were measured quantitatively. Non-essential fatty acids levels were increased and omega-3 fatty acids levels were decreased with the progress of deterioration of hepatic function. Regarding omega-6 fatty acids, C18:2 and 20:4 did not show any significant difference between the three groups and the control, and only C20:3 increased with the deterioration of liver dysfunction. The ratio of C20:3 (omega-6) to C20:4 (omega-6) was increased significantly with the progress of liver dysfunction. The activity of delta-5 desaturase was suspected to be suppressed in BA patients with poor liver function. The BA patients with poor bile flow did not show any decrease of omega-6 fatty acids in the plasma, but were at risk of developing omega-3 fatty acid deficiency.

Nuclear DNA content and nucleolar organizer regions in colorectal cancer.

The prognostic value of nuclear DNA content and argyrophilic nucleolar organizer regions (AgNOR) is still controversial in colorectal cancer. Sixty patients with colorectal cancer were studied by flow cytometric DNA analysis and AgNOR measurement, and their prognostic significance was tested. DNA index was closely linked to depth of invasion and lymph node metastasis, while AgNOR count did not correlate with such parameters. The survival curve was strongly influenced by depth of invasion, lymph node metastasis, and Dukes' stage but was not affected by DNA ploidy and AgNOR count. These results indicate that neither DNA ploidy nor AgNOR count correlates with survival of patients, although DNA ploidy is linked to progression of colorectal cancer.

Malignant lymphoma of the rectum treated preoperatively with hyperthermia and radiation.

A 58-year-old Japanese woman with primary malignant lymphoma of the rectum was treated preoperatively with radiation and intraluminal hyperthermia, after which abdominoperineal rectal amputation (Miles' operation) was done. The rectal tumor disappeared and there were no lymphoma cells in the resected specimens. The postoperative course was smooth and she is being followed in the outpatient department. At this writing, five years after the surgery, she remains well.

The distribution of lymph node metastases in right-sided colon cancer.

We reviewed the surgical results of 57 patients with right-sided colon carcinoma (RCC) with special reference to lymph node metastasis. In 45 cured patients, 25 showed no lymph node metastasis (n0), 19 showed a low or moderate degree of lymph node metastasis (n1, n2), and only one showed a high degree of lymph node metastasis (n3). As for the remaining 12 cases, the reasons that operation did not lead to a cure were liver or lung metastasis (66%), peritoneal spread (17%), or extensive lymph node metastasis (17%). Among these patients, only one may have died from insufficient lymph node dissection (R2 < n3). The presence of lymph node metastasis was predicted by the serum carcinoembryonic antigen level (> 3.0 ng/ml) and histologic type (other than well differentiated). These results indicate that complete removal of the group 1 and 2 nodes (R2 dissection) is a feasible operation for RCC.

Immunohistochemical expression of carbohydrate antigen 19-9 in colorectal carcinoma.

OBJECTIVES: Carbohydrate antigen 19-9 (CA19-9) is one of the most representative tumor markers in colorectal carcinomas. We studied the immunohistochemical expression of CA19-9 in primary colorectal carcinoma to identify its significance as a prognostic factor. METHODS: The avidin-biotin-peroxidase complex method was used for CA19-9 staining in sections from 149 patients with primary colorectal carcinoma. The data were studied by univariate and multivariate analyses. RESULTS: 86 tumors (56%) stained positively. The staining pattern was classified into three groups: group I (a stromal type, 22 tumors), group II (an apical and/or cytoplasmic type, 64 tumors), and group III (no staining, 63 tumors). Eight clinicopathologic variables showed a significant relationship with the staining pattern of CA19-9. The 5-yr survival rate of the group I subjects was significantly lower than that of the other two groups. With the multivariate analysis, the staining pattern of CA19-9 proved to be one of the independent prognostic variables. CONCLUSIONS: In addition to conventional prognostic factors, the staining pattern of CA19-9 is considered to be of value in predicting the prognosis of patients with colorectal carcinomas.

A clinicopathologic study of mucinous gastric carcinoma.

A clinicopathologic study of 42 mucinous gastric carcinomas (MGC) and 73 nonmucinous gastric carcinomas (NGC) was done. The tumor was defined as MGC when more than one half of tumor area had mucin pools. The 5-year survival rate for curatively treated patients was almost the same in MGC (58%) and NGC (56%), and clinicopathologic features, except for lymphatic permeation, showed no significant difference between MGC and NGC. Findings in MGC patients who died of a recurrence within 3 years included total gastrectomy, upper location, large size, infiltrative growth, extraserosal invasion, positive lymph node metastasis, more advanced stage, and a noncurative operation. There was no significant correlation between the degree of mucin content and other data, including the prognosis. Histologically, MGC were divided into well-differentiated and poorly differentiated types, according to the degree of glandular formation of the tumor cells. In patients with well-differentiated MGC, the age of onset was older, tumor growth was localized, and there were metastases to the liver. In patients with poorly differentiated MGC, the age of onset was younger, tumor growth was infiltrative, and there was peritoneal dissemination. These results show that the biologic behavior of MGC is similar to that of NGC and that the lesion basically is determined by the histologic subtype, not by the mucin content.

Multiple colorectal neoplasms in a young adult with hypogammaglobulinemia. Report of a case.

We report on a 22-year-old man with congenital hypogammaglobulinemia who developed multiple colorectal neoplasms. An immunodeficiency had been diagnosed in the patient since two years of age, and this time many tumors of the sigmoid colon and rectum were detected by barium enema and fiberscopy. Abdominoperineal resection was performed, and the resected specimen revealed 29 polyps, including 9 adenocarcinomas and 20 adenomas. The carcinomas, measuring 0.8 to 11.0 cm in size, showed various depths of invasion, and the adenomas, measuring 0.2 to 1.5 cm in size, showed various degrees of epithelial atypia. DNA analysis demonstrated that the tumors were heterogeneous, showing different DNA index and ploidy patterns. The pathogenetic relation between malignancy and immunodeficiency is also reviewed.

Vascular invasion of colorectal carcinoma readily visible with certain stains.

We made use of hematoxylin and eosin (H&E) stain, Verhoeff van-Gieson stain for elastic tissue (EVG), and factor VIII-related antigen (FVIII-RA) to stain tissues excised from 94 patients with colorectal carcinoma. Of these 94, 49 died of disease within two years (Group I), and 45 survived for five years or longer (Group II) after surgery. In the tissues from both groups, the use of EVG stain revealed a higher incidence of vascular invasion than was seen with H&E stain. In Group I, the rates were 28.6 percent and 61.2 percent with H&E and EVG, respectively, and those in Group II were 4.4 percent and 31.1 percent, respectively. Conversely, the FVIII-RA stain showed a decrease in the incidence of vascular invasion in both groups. In Group I, when vascular invasion was examined in EVG-stained tissues, the incidence was 81.3 percent in cases of hematogenous metastases and 23.5 percent in those without hematogenous metastases (P less than 0.01). These differences were not evident with H&E. When observing the site of vascular invasion in tissues of the colorectal wall stained with EVG, intramural and extramural types of vascular invasion were seen in 20 percent and 80 percent of cases in Group I and in 93 percent and 7 percent of those in Group II, respectively. Thus, not only the frequency, but also the site, of vascular invasion into the colorectal wall evidenced with EVG stain provides a more precise prediction of the recurrence of hematogenous metastases.

Surgical resection of pulmonary metastases from colorectal adenocarcinoma. Special reference to repeated pulmonary resections.

Pulmonary resection of metastatic lesions from colorectal adenocarcinoma was performed in 35 patients. The cumulative 5-year survival was 38%. The primary site of cancer was the colon in about half of the patients. Patients with a solitary metastasis or tumors smaller than 3 cm in diameter survived longer than did patients with multiple metastases or tumors larger than 3 cm but the differences were not significant. Other factors, including age, sex, histologic grade of tumor, location and stage of primary carcinoma, location of pulmonary metastases, disease-free interval, and type of pulmonary resection, had no apparent influence on survival time. The lung was the major site of recurrence following pulmonary resection. Seven patients underwent two or more pulmonary resections for metastasis from a colorectal carcinoma. At the time of last follow-up, four patients were alive and free of recurrent disease at 5, 34, 39, and 58 months after the second pulmonary resection. These data suggest that some patients will survive for a long time following pulmonary resection of colorectal metastases, and for highly selected patients, repeated pulmonary resection may further extend survival.

Immunohistochemical expression of carbohydrate antigen 19-9 in gastric carcinoma.

Immunohistochemical localization for carbohydrate antigen 19-9 (CA19-9) was studied in the gastric tissues from 115 patients with advanced gastric carcinoma. We compared two groups: 57 patients who died of recurrence or metastases within 2 yr (group I) and 58 patients who survived 5 yr or more after resection (group II). The staining patterns were classified into negative, apical, and/or cytoplasmic type and stromal type. Thirty-three cases (58%) of group I showed a stromal type, whereas only 17 cases (30%) of group II showed the same type. In undifferentiated type carcinoma, the stromal type was seen in 20 cases (65%) of group I and seven cases (23%) of group II. However, in differentiated type carcinoma, there was only a small difference in the appearance of stromal type between group I (50%) and group II (37%). The immunohistochemical localization for CA19-9 in the tumor tissues, particularly in undifferentiated carcinoma, will be useful in predicting the prognosis of the patients with advanced gastric carcinoma.

Ten-year survivors after surgical treatment and perioperative irradiation for esophageal carcinoma.

Ten of 150 patients with primary squamous cell carcinoma of the esophagus and surgically treated, survived for more than 10 years. All 10 underwent a complete resection of the primary tumor and extensive lymph node dissection plus perioperative irradiation. The clinicopathologic findings in these 10 patients were reviewed. Five were female. Seven of the tumors exceeded 6 cm in length; seven were early stage, and the remaining three were advanced stage tumors. Lymph node metastases were evident in three, lymph vessel permeation was recognized in four, and no vascular vessel permeation was seen in any tumor. Two tumors had a characteristic appearance of carcinoma with lymphoid stroma, suggesting a good prognosis. In six for which cytophotometric DNA analysis could be done, four were type II, two were type III, and none was type IV. Thus, a complete resection of the primary tumor and extensive lymph node dissection can lead to a long survival time even for those with an advanced primary esophageal carcinoma.

Distribution of basement membrane antigens in human esophageal lesions: an immunohistochemical study.

The distribution of basement membrane components, type-IV collagen and laminin, was studied immunohistochemically in human samples of normal, hyperplastic, dysplastic and carcinomatous esophageal tissue. The expression of basement membrane components in normal, hyperplastic, and mildly and moderately dysplastic mucosa was characterized by a thick, continuous and linear staining pattern. In severe dysplasia and carcinoma in situ, the basement membrane was thinner and occasionally discontinuous. The distribution of basement membrane in invasive carcinomas varied greatly; well-differentiated, cohesive tumors had a basement membrane, however, poorly-differentiated tumors showing irregular cords, or individual cell infiltration, lacked this membrane at the tumor-stromal interface. Many moderately-differentiated tumors showed probable immature assembly of basement membrane components. The expression of basement membrane was also influenced by the extent of stromal inflammation. The absence or presence (staining pattern) of basement membrane components in esophageal squamous-cell carcinoma did not correlate with the survival rate, but did correlate with the histologic differentiation of epithelial organization.

Sensitivity to heat and radiation of human rectal malignant tissues in vitro.

The sensitivity to heat and radiation of 22 rectal cancer tissues obtained at biopsy was studied using the in vitro succinate dehydrogenase inhibition test. The succinate dehydrogenase activity of tissue fragments was assayed after exposure at 43 degrees C (hyperthermia) for 20 hours, to radiation of 6 Gy, and to both heat (43 degrees C) and radiation (6 Gy). The sensitivity to each treatment was estimated by the percentage of succinate dehydrogenase activity of the treated cells compared with that of control cells. The mean plus or minus standard deviation of succinate dehydrogenase activity after exposure to radiation, heat, and both heat and radiation, was 84.7 +/- 12.6 percent, 52.9 +/- 20.7 percent, and 46.8 +/- 20.7 percent, respectively. The succinate dehydrogenase activities of heat-treated cells and both heat- and radiation-treated cells were significantly lower than that of the radiation-treated cells (P less than 0.01). The succinate dehydrogenase activities of heat plus radiation treated cells were the lowest in tissues from cancer lesions. Although the number was small, there was a correlation between this test and clinical outcome in seven of nine cases. Thus, preoperative therapy of hyperthermia plus radiotherapy is expected to be effective for treating patients with rectal cancer.