Effect of direct retainer and major connector designs on RPD and abutment tooth movement dynamics.

Designs of removable partial dentures are suggested to affect the mobility of abutment teeth and removable partial denture (RPD) during oral functions. This study aimed to examine the effect of direct retainer and major connector designs on RPD dynamics under simulated loading. Six different Kennedy class II maxillary RPDs were fabricated on a maxillary model. These dentures involved 3 different direct retainers (wrought-wire clasp, RPA clasp, and conical crown telescopic retainer) and 2 different major connectors (Co-Cr major connector and heat-cured acrylic resin with a metal strengthener). Using an experimental model with simulated periodontal ligaments and mucosa that were fabricated using silicone impression material, three-dimensional displacements of the RPDs were measured under a simulated 30-N loading with a displacement transducer type M-3. Significant effects of "direct retainer design" on bucco-palatal displacements and "major connector" on mesio-distal displacements were revealed by 2 x 3 two-way analysis of variance of abutment teeth movements (P < 0.001 and P = 0.002, respectively). Additionally, analysis of variance of RPD displacements revealed significant effects of "direct retainer design" on corono-apical displacements and "major connector" on mesio-distal displacements (P = 0.001 and P = 0.028, respectively). Rigid direct retainers and rigid major connectors decrease the movements of both abutment tooth and RPD.

Clinical significance of midkine expression in pancreatic head carcinoma.

Midkine (MK) is a heparin-binding growth factor and a product of a retinoic acid-responsive gene. Midkine is overexpressed in many carcinomas and thought to play an important role in carcinogenesis. However, no studies have been focussed on the role of MK in pancreatic carcinoma. This study sought to evaluate the clinical significance of MK expression in pancreatic head carcinoma, including the relationship between immunohistochemical expression and clinicopathologic factors such as prognosis. Immunohistochemical expression of MK and CD34 was evaluated in pancreatic head carcinoma specimens from 75 patients who underwent surgical resection. Midkine was expressed in 53.3% of patients. Midkine expression was significantly correlated with venous invasion, microvessel density, and liver metastasis (P=0.0063, 0.0025, and 0.0153, respectively). The 5-year survival rate was significantly lower for patients positive for MK vs patients negative for MK (P=0.0073). Multivariate analysis revealed that MK expression was an independent prognostic factor (P=0.0033). This is the first report of an association between MK expression and pancreatic head carcinoma. Midkine may play an important role in the progression of pancreatic head carcinoma, and evaluation of MK expression is useful for predicting malignant properties of pancreatic head carcinoma.

Epstein-Barr virus involvement is mainly restricted to lymphoepithelial type of gastric carcinoma among various epithelial neoplasms.

To demonstrate the association of Epstein-Barr virus (EBV) with primary epithelial neoplasms in the south part of Kyushu, Japan, 761 carcinomas consisting of 75 lung, 61 breast, 107 esophagus, 102 colon, 58 pancreas, 45 thyroid, and 313 gastric cancers were examined by EBER-1 in situ hybridization. EBER-1 was detected in 23 cases (7.3%) out of 313 gastric carcinomas, while none of the other carcinomas was positive for EBER-1. Twenty-eight (9.4%) out of 313 gastric carcinomas were differentiated poorly to moderately carcinomas with prominent lymphoid cell infiltration, similar to so-called lymphoepithelioma-like carcinoma, and 19 cases (67.9%) were positive for EBER-1. Although two (2.6%) and 11(10.3%) out of 75 lung and 107 esophagus carcinomas were so-called lymphoepithelioma-like carcinomas, respectively, but EBER-1 was not detected in other epithelial neoplasms that originated from the lung, esophagus, breast, colon, pancreas, and thyroid in the south of Kyushu, Japan. As a result, EBV was associated with only some gastric carcinomas but not with other epithelial neoplasms originating from the lung, esophagus, breast, colon, pancreas, and thyroid in southern Japan.

Invariant chain expression in gastric cancer.

Invariant chain (Ii) is a chaperone molecule that inhibits the binding of endogenous antigens to HLA class II. The tumor cell with overexpressed Ii chain is thought to escape attacking cytotoxic lymphocytes by suppressing the host immune. However, the relationship between Ii expression by the tumor and clinicopathological factors in gastric cancer remains unclear. We studied 126 patients with gastric cancer who had undergone curative gastrectomy at Kagoshima University Hospital between 1988 and 1997. In order to detect Ii and HLA-DR expression by tumor cells, immunohistochemical staining with anti-CD74 and anti-HLA-DR antibodies were performed by avidin-biotin peroxidase complex method. The 126 patients studied were divided into two groups based on Ii expression. Ii and HLA-DR were expressed both on the surface and in the cytoplasm of tumor cells and tumor infiltrating lymphocytes. A total of 48 patients were identified as Ii positive, while the remaining 78 patients were Ii negative. Ii expression negatively correlated with the depth of invasion of the tumor as well as the patients' clinical stage. Ii expression was negatively correlated with HLA-DR expression. Patients with Ii negative expression had significantly better surgical outcomes than those with Ii positive expression (P<0.05). Ii expression in gastric cancer affected surgical outcome and Ii expression was negatively correlated with depth of invasion and HLA-DR expression. Ii expression in gastric cancer may be a prognostic factor related to suppressive effects on host immune responses to tumor cells.

Surgical maneuvers enhance molecular detection of circulating tumor cells during gastric cancer surgery.

OBJECTIVE: To evaluate the relation between the presence of cancer cells in blood according to the time course during a surgical procedure and liver metastases in patients with gastric cancer. SUMMARY BACKGROUND DATA: Several studies have reported on the detection of circulating cancer cells in blood by reverse transcriptase-polymerase chain reaction (RT-PCR). However, few reports have examined the relation between molecular detection of circulating cancer cells according to the time course during a surgical procedure and blood-borne metastases. METHODS: Blood samples from 57 patients with gastric cancer were obtained from the portal vein, peripheral artery, and superior vena cava before and after tumor dissection. After total RNA was extracted from each blood sample, carcinoembryonic antigen (CEA)-specific RT-PCR was performed. RESULTS: CEA-mRNA was detected in the blood of 21 (36.8%) of the 57 patients. CEA-mRNA was not detected in the blood obtained from 15 healthy volunteers and 15 patients with benign disease. The positive rate increased in proportion to the depth of tumor. The incidence of positive CEA-mRNA did not differ among the various sites of blood sampling. The appearance of circulating cancer cells was related to the surgical maneuver. A significant relation was found between the detection of CEA-mRNA and blood-borne metastases. CONCLUSIONS: A high incidence of positive CEA-mRNA was found in the blood during gastric cancer surgery. Surgical maneuvers are a possible cause of hematogenous metastasis. The authors found that patients with positive CEA-mRNA had a high risk of blood-borne metastasis even after curative resection.

Effect of neoadjuvant chemotherapy for lymph node micrometastasis and tumor cell microinvolvement in the patients with esophageal carcinoma.

Micrometastasis (MM) and tumor cell microinvolvement (TCM) in the lymph node were immunohistochemically evaluated using the cytokeratin (CK) antibody between a surgery group (n=20; 929 lymph nodes) and a chemotherapy group (n=20; 1052 lymph nodes). The incidence of MM+/-TCM in the surgery and chemotherapy groups was 50.0 (10/20) and 55.0% (11/20), respectively. Limiting the analysis to TCM alone revealed that the incidence in the chemotherapy group (10.0%; 2/20) was significantly lower than that in the surgery group (40.0%; 8/20; P=0.032). Preoperative chemotherapy in this regime was not effective, except for some patients with TCM alone.

Clinical impact of intratumoral natural killer cell and dendritic cell infiltration in gastric cancer.

Intratumoral natural killer cells (NKC) and dendritic cells (DC) may affect the clinical features of various gastrointestinal cancers. However, the relationship between intratumoral NKC and DC remains unclear. We examined 169 patients with gastric cancer who underwent gastrectomy at Kagoshima University Hospital. Immunohistochemical staining of CD57 and S-100-protein was performed to evaluate NKC and DC infiltration, respectively. A total of 25 areas containing pericancerous tissue were selected for determining the number of NKC and DC under high power microscopy (x400). Patients were classified into two groups according to NKC and DC population. Intratumoral lymphocytic infiltration was also calculated in 15 areas with a high power (x400) objective. The degree of NKC and DC infiltration was gradually decreased according to the progression of nodal involvement. Patients with many NKC infiltration had a lower positivity of lymph node metastasis and lymphatic invasion than patients with little NKC infiltration. DC infiltration was also negatively correlated with depth of invasion, lymph node metastasis and curativity. DC infiltration was positively correlated with lymphocytic infiltration (P=0.01. r=0.6). The 5-year survival rates of patients with many NKC infiltration and patients with DC many infiltration were 75 and 78%, respectively, both of which were significantly better than that of patients with little NKC and DC infiltration (P<0.05). NKC may be activated without DC or intratumoral lymphocytes. Intratumoral NKC may act as an independent immunologic effector against tumor cells, unlike DC.

Serum midkine levels are increased in patients with various types of carcinomas.

The level of expression of midkine (MK), a heparin-binding growth factor, is increased in many types of human carcinomas. An enzyme-linked immunoassay, which utilizes a combination of rabbit and chicken antibodies revealed that serum MK level in the controls (n = 135) was 0.154 +/- 0.076 (mean +/- SD) ng ml(-1)with an apparent cut-off value as 0.5 ng ml(-1). Serum MK level was significantly elevated in the cancer patients (n = 150) (P< 0.001); 87% of the patients showed levels of more than 0.5 ng ml(-1). All ten types of cancer examined showed a similar profile of serum MK level. There was no or weak correlation between C-reactive protein level, a marker of inflammation, and serum MK level. Furthermore, in case of gastric carcinoma and lung carcinoma, patients with stage I carcinoma already showed elevated serum MK levels. The present results indicated that serum MK could serve as a general tumour marker with a good potential for clinical application.

Intranodal antitumor immunocyte infiltration in node-negative gastric cancers.

The status and role of immunocytes and dendritic cells in regional lymph nodes in patients with gastric cancer are examined in this study. Forty-nine patients with gastric cancer who underwent curative resection were enrolled in the present study. These patients had no lymph node metastases according to a histological examination. The infiltration of natural killer (NK) cells, dendritic cells, and MIB-1-positive immunocytes was investigated. Based on the Japanese Classification of Gastric Carcinoma, regional lymph nodes were divided into three compartments: (a) compartment 1 (lymph node station numbers 1-6); (b) compartment 2 (lymph node station numbers 7-12); and (c) compartment 3 (lymph node station numbers 14 and 16). Dendritic cells and MIB-1-positive immunocytes infiltrated compartment 1 lymph nodes in increased numbers compared with the lymph nodes of compartments 2 or 3 (P < 0.05). Conversely, intranodal NK cell infiltration did not differ significantly among the three compartments. The incidence of intranodal dendritic and MIB-1-positive cell infiltration in patients with submucosal gastric cancer was significantly higher than in patients with tumors that invaded beyond the muscularis propria. The decreased expression of these immunological markers correlated well with recurrent disease, regardless of tumor depth. The immunocyte level is higher in lymph nodes near the primary tumor (compartment 1) than in those that are distant from the tumor (compartments 2 and 3). This pertains to all three markers, i.e., NK, dendritic, and MIB-1-positive cells. Unlike dendritic and MIB-1-positive cells, intratumoral infiltration of NK cells did not correlate well with either lymph node compartment or the depth of tumor invasion. The degree of NK cell infiltration may be directly associated with antitumor effects, especially in compartment 1. A decrease in all three markers is associated with tumor recurrence.

Detection and clinical significance of lymph node micrometastasis determined by reverse transcription-polymerase chain reaction in patients with esophageal carcinoma.

We investigated micrometastasis in lymph nodes by detecting carcinoembryonic antigen (CEA) mRNA. A total of 400 lymph nodes obtained from 21 patients with esophageal carcinoma were examined by CEA-specific reverse transcription-polymerase chain reaction (RT-PCR). Serial sections of positive lymph nodes were reexamined histologically and immunohistologically. Twenty-seven lymph nodes of 11 patients were diagnosed as being positive by conventional histologic examination. CEA-mRNA positivity was found in 18 of 21 patients. Among 373 histologically negative nodes, 79 (21.2%) were positive for CEA mRNA. Of these, micrometastasis was detected in 2 by histological reexamination and in 11 by immunohistochemical staining using cytokeratin antibody. Two of 6 RT-PCR-positive patients (33.3%) had recurrent disease. Four of 11 patients (36.4%) whose nodal involvement was discovered by routine histological examination also had recurrent cancer. CEA-specific RT-PCR detected micrometastasis in lymph nodes at a higher rate than histological or immunohistochemical analysis of serial sections. Since the incidence of CEA-mRNA positivity is high in the lymph nodes of esophageal cancer patients except for those with early cancer, these patients should be treated with adjuvant therapy.

Prognostic value of intratumoral natural killer cells in gastric carcinoma.

BACKGROUND: Natural killer (NK) cells are a group of effector cells that act nonspecifically against tumor cells. The correlation between intratumoral NK cell infiltration and clinicopathologic features remains unclear. METHODS: The authors selected 146 patients with gastric carcinoma who underwent gastrectomy at Kagoshima University Hospital between 1985-1995. Immunohistochemical staining with the CD57 antibody was performed for the evaluation of NK cell infiltration. A total of 25 areas containing CD57 positive cells were selected and the number of NK cells were counted (magnification, x200). The patients were divided into 2 groups: patients with a high level of NK infiltration (n = 39) (>25 NK cells/25 high-power fields [HPF]) and patients with a low level of NK infiltration (n = 107) (<25 NK cells/25 HPF). Intratumoral lymphocytic infiltration also was counted in 25 areas at a magnification of x200. Patients were classified into a high infiltrating lymphocyte (IL) group (n = 69) (>150 cells/HPF) and a low IL group (n = 77) (<150 cells/HPF). The Kaplan-Meier curve was used to analyze surgical outcome. Multivariate analyses were performed to evaluate prognostic factors. RESULTS: Patients with a high level of NK infiltration had a higher rate of early gastric carcinoma, fewer metastases to the lymph nodes (P < 0.01), and less lymphatic invasion (P < 0.05) than patients with a low level of NK infiltration. NK cell infiltration also was found to correlate with depth of invasion, clinical stage, and venous invasion. There was no correlation between NK cells and lymphocytic infiltration (P = 0.07; correlation coefficient = 0.15). The 5-year survival rate of patients with a high rate of NK infiltration was 78%, which was significantly better than that of patients with a low level of NK infiltration (P < 0.01). Multivariate analysis did not show NK cell infiltration to be a significant prognostic factor. Combination analysis of the number of NK cells and lymphocytic infiltration was shown to be an independent prognostic factor (P = 0.02; hazard ratio = 1.32). CONCLUSIONS: Patients with a high level of NK infiltration were found to have a better prognosis than those with a low level of NK infiltration. Combination analysis with lymphocytic infiltration may provide useful information regarding the immunologic condition of patients with gastric carcinoma.

Molecular detection of circulating cancer cells during surgery in patients with biliary-pancreatic cancer.

BACKGROUND: It remains unclear whether surgical treatment for biliary-pancreatic cancers provokes the hematogenous dissemination of cancer cells. The aim of this study was to detect circulating cancer cells in the blood stream before and during tumor resection for biliary-pancreatic cancer. METHODS: We analyzed blood samples obtained perioperatively from the portal vein, peripheral artery, and superior vena cava, using a carcinoembryonic antigen (CEA)-specific nested reverse transcriptase-polymerase chain reaction. RESULTS: CEA-mRNA expression was detected in the blood of 21 (52.5%) of 40 patients with biliary-pancreatic cancer. The patients with detectable CEA-mRNA expression included 8 (42.1%) of 19 with bile duct cancers and 13 (61.9%) of 21 with pancreatic cancers. CEA-mRNA expression was not detected in blood obtained from 15 healthy volunteers and 15 patients with benign disease. The positive rate of CEA-mRNA of advanced clinical stage (TNM pStage III and IV) showed higher than that of early stage (pStage I and II; P <0.05). Tumor resection increased significantly the positive rates of CEA-mRNA in the blood stream of three kinds of vessel. CONCLUSIONS: Surgical procedures provoke the hematogenous dissemination of cancer cells perioperatively. Therefore, new strategies during operations to prevent liver metastases are needed to improve the survival of patients with biliary-pancreatic cancer.

Carcinomatous lymphatic invasion in early gastric cancer invading into the submucosa.

BACKGROUND: Lymphatic invasion is a risk factor for lymph node metastases in patients with gastric cancer. No studies have been reported, however, on the correlation between lymphatic invasion and lymph node metastasis in early gastric cancer invading into the submucosa. METHODS: We performed a retrospective analysis of lymphatic invasion in 170 patients with early gastric cancer invading into the submucosa. RESULTS: Lymphatic invasion was found in 76 patients. Lymphatic invasion correlated significantly with the presence of lymph node metastasis and vascular invasion (P < .05) and with the degree of cancerous submucosal involvement (P < .05). The presence of lymph node metastasis also correlated with the grade of submucosal invasion and lymphatic invasion. The 5-year survival of patients with lymphatic invasion was poorer than that of patients without lymphatic invasion (P < .05). Node-negative patients had similar survival, regardless of the presence of lymphatic invasion. All patients with severe lymphatic invasion had sm3 invasion and lymph node metastases. CONCLUSION: Although lymphatic invasion is the first stage of lymph node metastasis, lymphatic invasion in itself does not have clinical importance except for severe invasion in early gastric cancer. It is possible to predict lymph node metastases from the combined evaluation of degree of lymphatic invasion and submucosal involvement of the tumor in patients with early gastric cancer invading into the submucosa.

Carcinomatous infiltration into the submucosa as a predictor of lymph node involvement in early gastric cancer.

The clinicopathologic features of 114 patients with resectable early gastric cancer (EGC) invading the submucosa were examined retrospectively with respect to lymph node involvement and the possibility of performing a minimally invasive operation. Patients were divided into node-positive (n = 25) and node-negative (n = 81) groups. Among several pathologic factors, the diameter of the tumor and lymphatic involvement were significantly correlated with nodal involvement. Within the submucosal layer the depth of invasion and the horizontal cancerous expansion also correlated with lymph node disease (p < 0.05). The size of the tumor did not correlate with the length of submucosal infiltration (r = 0.12, p = 0.1). Patients with both slight invasion into the submucosa and less than 5 mm of horizontal expansion were often negative for lymph node involvement and thus may benefit from local surgery as an alternative to gastrectomy.

Truncated midkine as a marker of diagnosis and detection of nodal metastases in gastrointestinal carcinomas.

Midkine (MK) is a growth factor identified as a product of a retinoic acid-responsive gene. A truncated form of MK mRNA, which lacks a sequence encoding the N-terminally located domain, was recently found in cancer cells. We investigated the expression of the truncated MK mRNA in specimens of 47 surgically removed human gastrointestinal organs using polymerase chain reaction. Truncated MK was not detected in all of the 46 corresponding non-cancerous regions. On the other hand, this short MK mRNA was expressed in the primary tumours in 12 of 16 gastric cancers, 8 of 13 colorectal carcinomas, five of nine hepatocellular carcinomas, two of two oesophageal carcinomas and one ampullary duodenal cancer. In addition, truncated MK was detectable in all of the 14 lymph node metastases but in none of three metastatic sites in the liver, suggesting that truncated MK mRNA could become a good marker of nodal metastases in gastrointestinal tract.

[Experience of 7 cases with home parenteral nutrition in our hospital].

We have experienced 7 patients with home parenteral nutrition (HPN), (including 3 failure cases). Four were benign disease and 3 were malignant. The HPN was given for 0 to 316 days. In 3 cases, we could not allow them to leave the hospital. All 3 cases involved malignant disease. The catheter was removed in only 1 case because of infection. Technical complications due to catheterization or catheter maintenance were not found in the other 6 cases. For successful management of HPN, the following 3 points are necessary for patients, family or doctors. 1) Patients and their family must understand their disease and condition. 2) Patients and their family have great hopes of spending their final days at home. 3) Doctors should have more concern for HPN.

Comparison of p53 expression in proximal and distal gastric cancer: histopathologic correlation and prognostic significance.

BACKGROUND: The overexpression of p53 has been found to be correlated with prognosis of some carcinomas, including gastric cancer, but no studies have reported on its relationship to the location of gastric cancer. In the present study, we compared the p53 expression of proximal and distal gastric cancer concerning histopathology and prognosis. METHODS: A total of 170 tumors in the patients with proximal (80 cases) and distal (90 cases) gastric cancer were studied by immunohistochemical methods. RESULTS: p53 immunopositivity was detected in 28.8% of all tumors. The p53-positive expression in proximal gastric cancer was higher than in distal gastric cancer (38.8% vs. 20.0%, p < 0.05). A 5-year survival analysis showed that there is no significant difference between tumors that are p53 positive and p53 negative. No correlation was found between p53 expression and histopathology of gastric cancer. CONCLUSION: p53 nuclear staining is not useful as a prognostic indicator or as a parameter in gastric cancer.

Extranodal connective tissue invasion and the expression of desmosomal glycoprotein 1 in squamous cell carcinoma of the oesophagus.

We investigated extranodal connective tissue involvement (ECTI) in 39 patients with oesophageal carcinoma. Both the primary tumour and ECTI were immunohistochemically examined using the monoclonal antibody 32-2B for desmosomal glycoprotein 1 (DG1). Connective tissue carcinoma deposits were identified as cells within small lymph nodes, as lymphatic or venous vessel invasion or as widespread invasion beyond the capsule of metastatic lymph nodes. These histological findings were present in at least one area in 20 of 39 patients (51.3%). DG1 immunostaining intensity by tumour was graded as DG1 (++), DG1 (+) or DG1 (-). DG1 (+) or DG1 (-) primary tumours demonstrated lymph node metastases and ECTI more frequently than DG1(++) tumours (P<0.05). Among 17 patients in whom DG1 immunohistochemistry was performed on ECTI, there were three DG1(++), five DG1(+) and nine DG1(-) patients. The DG1 expression of ECTI was equal to or less intense than the primary tumour. These results indicate that reduction or loss of DG1 expression may promote ECTI and lymph node metastases. One should be aware of the potential for ECTI in oesophageal carcinomas. In the future, adjuvant therapy may be advisable for some oesophageal carcinomas based on the phenotype of individual cancer cells, including expression of DG1.

The expression of truncated MK in human tumors.

Midkine (MK) is a heparin binding growth/differentiation factor different from fibroblast growth factors (FGFs), and is largely composed of two domains which are found by a folded polypeptide chain interconnected by disulfide bridges. Polymerase chain reaction revealed the presence of a short MK mRNA in 7 among 12 human tumor cells which expressed MK mRNA. All of 4 pancreatic carcinoma cell lines expressed the short species in addition to the full size mRNA. The short mRNA lacked an exon and resulted in the lack of a more N-terminally located domain. The truncated form of MK was found also in some surgically removed specimens of human tumors, but not in noncancerous tissue.

Increased midkine gene expression in human gastrointestinal cancers.

Midkine (MK) is a product of a retinoic acid-responsive gene, and is a novel growth differentiation factor. We examined the expression of the MK gene in specimens of 47 surgically removed human carcinomas of the gastrointestinal organs, namely, gastric, colorectal, hepatocellular, pancreatic, esophageal, ampullary duodenal and bile duct carcinomas. In most cases, the MK mRNA level was higher in cancer specimens than in the corresponding non-cancerous tissues. Furthermore, MK mRNA was more highly expressed in the colon adenocarcinoma lesion than in the adenoma lesions, in the two familial polyposis cases. While MK mRNA was not detected in the normal liver, it became detectable in cirrhotic tissues in 2 of 4 cases, and its expression was increased in the cancerous tissues. Thus, the increase of MK mRNA level is a phenomenon seen in many human gastrointestinal carcinomas. The increased expression of the MK gene in gastric carcinoma was significantly more prominent in well and moderately differentiated adenocarcinomas than in poorly differentiated adenocarcinomas and signet ring cell carcinomas.