Effects of an immuno-enhanced diet containing antioxidants in esophageal cancer surgery following neoadjuvant therapy.

Neoadjuvant therapy-induced immunological deterioration may be a key factor in postoperative morbidity in patients with esophageal cancer. This study aimed to determine the effects of perioperative feeding with an immuno-enhanced diet on immune competence in patients treated with neoadjuvant therapy followed by surgery. Because an immuno-enhanced diet that contained several antioxidants was used, perioperative oxidative stress and the effects of the immuno-enhanced diet on this stress were also investigated. Of 39 patients with esophageal cancer who underwent similar surgical procedures, 26 patients who received chemotherapy or chemoradiation therapy before surgery were randomly divided into two groups: group 1 (n= 14) was given an immuno-enhanced diet for 5 days before surgery, and group 2 (n= 12) received no enteral feeding products before surgery. Group 3 (n= 13) consisted of patients that did not receive neoadjuvant therapy and received no enteral feeding products before surgery. Several markers for coagulation and fibrinolysis were determined and immunological assessments were performed for each patient. To measure reactive oxygen metabolites and the total antioxidant capacity, diacron-reactive oxygen metabolites (d-ROMs) and OXY-adsorbent tests were performed using a free radical elective evaluator. Significant depression in lymphocyte numbers was observed in groups 1 and 2 before and early after surgery as compared to group 3. Numbers of B cells, CD4/CD8 ratio, and phytohemagglutinin-induced lymphocyte transformation tests were also significantly decreased in groups 1 and 2 on postoperative day 1. Fibrin and fibrinogen degradation products were significantly elevated in group 2 compared to group 1. d-ROMs and OXY-adsorbent test values were elevated before surgery and were decreased transiently early after surgery. Compared to groups 2 and 3, d-ROMs values were significantly lower in group 1 patients throughout the postoperative period, while OXY-adsorbent test values were significantly higher in group 2 patients. Oxidative index was significantly suppressed in group 1 compared to group 3. No significant intergroup differences were observed with regard to morbidity after surgery. Although the baseline levels of immunological function might have been different because of less-advanced cancer stages in group 3, neoadjuvant therapy significantly affected several immunological parameters. Preoperative administration of an immuno-enhanced diet did not significantly prevent neoadjuvant therapy-induced immunological deterioration prior to esophageal cancer surgery. Patients with esophageal cancer had elevated levels of oxidant and antioxidant activities before surgery, which were transiently decreased early after surgery. Although the underlying mechanisms for these perioperative changes are unclear, this study showed that an immuno-enhanced diet containing several antioxidants may reduce oxidative stress following esophageal cancer surgery. After these mechanisms are studied further, oxidative stress control may become another tool for perioperative management to reduce morbidity after esophageal cancer surgery.

Reduction rate of lymph node metastasis as a significant prognostic factor in esophageal cancer patients treated with neoadjuvant chemoradiation therapy.

Tumor regression is used widely as a measure of tumor response following radiation therapy or chemoradiation therapy (CRT). In cases of esophageal cancer, a different pattern of tumor shrinkage is often observed between primary tumors and metastatic lymph nodes (MLNs). Regression of MLNs surrounded by normal tissue may be a more direct measure of the response to CRT than regression of a primary tumor as exfoliative mechanical clearance does not participate in shrinkage of MLNs. In this study we evaluated the significance of the reduction rate (RR) of MLNs as a prognostic factor in esophageal cancer patients treated with neoadjuvant CRT. Forty-two patients with marked MLNs were selected from 93 patients with esophageal carcinoma who had received neoadjuvant CRT. The RRs of the primary tumor and the MLNs were calculated from computed tomography scans. In 20 patients, surgical resection was carried out following CRT. Univariate analysis was used to determine which of the following variables were related to survival: size of the primary tumor and MLNs; RRs of both lesions; degree of lymph node (LN) metastasis; clinical stage; and surgical resection. Multivariate analysis was then performed to assess the prognostic relevance of each variable. The primary tumor was larger than the MLNs in 69% of patients before CRT and in 40% of patients after CRT. In 79% of the patients, the RR of the primary tumor was greater than the RR of the MLNs. The results of the univariate analyses showed that a high RR of the MLNs and surgical resection after CRT were associated with significantly improved survival. The multivariate analysis demonstrated that the RR of MLNs had the strongest influence on survival. The RR of LN metastasis should be evaluated as an important prognostic predictor in patients with marked LN metastasis of esophageal cancer treated with CRT.

Types of programmed cell death: two variants expressed by neonatal murine hepatocytes.

Neonatal livers examined with the terminal transferase-mediated dUTP nick end labeling (TUNEL) method contained numerous positive cells. Although the majority of dying cells are either hematopoietic cells including erythroids and granulocytes or macrophages, a few hepatocytes were also positive. As for the ultrastructural features of these dying hepatocytes, two different types, type I and II, could be identified. The early features of type I appeared in the cytoplasm, which was characterized by dilated rough endoplasmic reticulum, and the cell fragments displayed a round, foamy appearance. Type II was characterized by nuclear compaction and margination of heterochromatin resulting in the formation of sharply circumscribed masses, followed by the condensation of the cytoplasm. The cell death of type I, characterized by the formation of massive vacuolization of the endoplasmic reticulum, corresponds to cytoplasmic type degeneration or nonapoptotic death, while that of type II corresponds to nuclear type cell death or classical apoptotic death. In the two types of programmed cell death, the incidence of nonapoptotic cell death was much higher than that of classical apoptosis in neonatal murine hepatocytes.

[Alterations in neuroepithelial intermediate filaments during neurogenesis in the chick cervical spinal cord].

Intermediate filament proteins including nestin, vimentin and neurofilament were immunohistochemically studied during neurogenesis in the chick cervical spinal cord from stages 8 to 28. At stage 8, neuroepithelial cells of the neural groove contained a large amount of nestin in their cytoplasm and a little vimentin in the basal cytoplasmic areas, and no neurofilaments could be recognized at all. At stage 10, there was a marked decrease in nestin expression in the neural groove, and there was an increase in vimentin in neuroepithelial cells. At stage 15, when the neural tube was formed, small oval neuroblasts appeared in the peripheral area of the neuroepithelium. By employing double-immunostaining, three different neuroblasts could be identified; vimentin-positive and neurofilament-negative cells, neurofilament- and vimentin-double-positive cells, and neurofilament-positive and vimentin-negative cells. During the neuroblast stage, intracellular intermediate filaments were relayed from vimentin to neurofilaments. At stage 20, large polygonal cells containing a large number of neurofilaments could be recognized in the enlarged basal plate of the neural tube. At stage 28, neuronal processes developed in large polygonal cells and, although the staining intensity of the neurofilaments was slightly decreased in the soma, the neuronal processes contained a large number of neurofilaments. During neurogenesis in the chick cervical spinal cord, the intermediate filaments, nestin and vimentin, are present in neuroepithelial cells. During the neuroblast stage, vimentin and neurofilaments are observed together for a short time. Finally, in polygonal neurons, only neurofilaments are observed.

[Keratin filaments in epithelial cells of the excretory ducts of rabbit submandibular glands--an immunohistochemical and ultraimmunohistochemical study].

To clarify the roles of various keratin proteins, the distributions of eight keratin intermediate filament proteins (keratins 7, 8, 10, 13, 14, 18, 19 and 20) in the epithelial cells of the excretory ducts of rabbit submandibular glands were studied immunohistochemically and ultraimmunohistochemically. The epithelia of excretory ducts were composed of columnar cells and basal cells. In the columnar cells, intermediate filaments formed a network at the apical area, that is, an apex network connected with desmosomes. Keratins 7, 18 and 20 were detected in the upper layer of the network and keratins 8, 18 and 20 in the lower layer. The intermediate filaments containing keratin 7 were also connected with hemidesmosomes on the basal side. Keratins 7, 18 and 20 were found throughout the entire cytoplasm of the columnar cells. Keratins 8 and 14 were expressed near the nucleus, forming a ring-like structure around the Golgi apparatus in the columnar cells. In the basal cells, by contrast, the intermediate filaments were concentrated around the nucleus, forming a juxtanuclear network which contained keratin 10. Keratin 13 was detected between the juxtanuclear network and the cell membrane, and was connected with both desmosomes and hemidesmosomes. Kratin 7 filaments were contained throughout the entire cytoplasm of the basal cells. These results suggested that different functional subsets of keratin filaments could be distinguished in the epithelial cells of the excretory ducts of the submandibular glands. In the columnar cells, keratins 7, 8, 18 and 20 play a role in cell-cell contact or cell-matrix contact, and both keratins 8 and 14 seem to be involved in the structure of the Golgi apparatus. In the basal cells, keratin 10 may serve to position and anchor the nucleus within the cell, and keratin 13 plays a role in cell-cell and cell-matrix contacts.

[Vimentin and neuroepithelial cell differentiation in the spinal cord of chick embryos: an immunohistochemical study].

Using vimentin immunohistochemical staining, the differentiation processes of neuroepithelium in the neural tube were examined in chick embryos from stages 8 through 28. At an early stage of the neural groove, stage 8, no morphological differences could be found among the neuroepithelial cells, but vimentin staining allowed us to identify four different regions in the groove wall. The epithelial cells in the ventral wall exhibited moderate staining of vimentin, and vimentin was detected in the basal and middle cytoplasmic areas. A weak staining limited to the basal cytoplasm was observed in the dorsal wall. In contrast, epithelial cells in the median hinge region and in the lateral edge of the neural groove had little vimentin. On the basis of this vimentin staining, four similar regions could also be observed in the neuroepithelium of the neural tube at stage 12; the ventral wall, dorsal wall, floor plate and roof plate. Prior to the morphological changes in the neuroepithelial cells, vimentin expression showed dramatic changes, and our immunohistochemical data suggest that cell differentiation into motor areas and sensory areas starts at an early stage of the neural groove.