Survival outcomes of 220 consecutive patients with three-staged thoracoscopic esophagectomy.

Patients with thoracic esophageal cancer are often treated by minimally invasive esophagectomy. However, the long-term survival benefits of minimally invasive esophagectomy remain unclear. Two approaches are available for thoracoscopic surgery: one with the patient in the left lateral decubitus position (LLDP), and the other with the patient in the prone position (PP). We investigated the survival benefit of thoracoscopic esophagectomy according to the tumor stage and patient position during the thoracoscopic procedure. We reviewed the records of 220 consecutive patients with esophageal cancer treated from 1998 to 2012. In total, 146 and 74 patients were treated with thoracoscopic esophagectomy in the LLDP and PP, respectively. No patients were initially proposed to be candidates for esophagectomy by thoracotomy during the study period. Data collection was performed with a focus on survival and recurrent disease. Among all the 220 patients, the overall 5-year survival rates were 83.7%, 74.1%, 45.5%, 78.6%, 44.2%, 29.4% and 24.3% in the patients with pStage IA, IB, IIA, IIB, IIIA, IIIB and IIIC disease, respectively. Despite the greater number of dissected mediastinal lymph nodes in the PP procedure, there were no significant differences in the survival curves between the LLDP and PP procedures. The long-term results of thoracoscopic esophagectomy are comparable and acceptable. The PP procedure was not confirmed to offer a superior survival benefit to the LLDP procedure in this retrospective study.

3-T MRI safety assessments of magnetic dental attachments and castable magnetic alloys.

OBJECTIVES: To assess the safety of different magnetic dental attachments during 3-T MRI according to the American Society for Testing and Materials F2182-09 and F2052-06e1 standard testing methods and to develop a method to determine MRI compatibility by measuring magnetically induced torque. METHODS: The temperature elevations, magnetically induced forces and torques of a ferromagnetic stainless steel keeper, a coping comprising a keeper and a cast magnetic alloy coping were measured on MRI systems. RESULTS: The coping comprising a keeper demonstrated the maximum temperature increase (1.42 °C) for the whole-body-averaged specific absorption rate and was calculated as 2.1 W kg⁻¹ with the saline phantom. All deflection angles exceeded 45°. The cast magnetic alloy coping had the greatest deflection force (0.33 N) during 3-T MRI and torque (1.015 mN m) during 0.3-T MRI. CONCLUSIONS: The tested devices showed minimal radiofrequency (RF)-induced heating in a 3-T MR environment, but the cast magnetic alloy coping showed a magnetically induced deflection force and torque approximately eight times that of the keepers. For safety, magnetic dental attachments should be inspected before and after MRI and large prostheses containing cast magnetic alloy should be removed. Although magnetic dental attachments may pose no great risk of RF-induced heating or magnetically induced torque during 3-T MRI, their magnetically induced deflection forces tended to exceed acceptable limits. Therefore, the inspection of such devices before and after MRI is important for patient safety.

Gemcitabine synergistically enhances the effect of adenovirus gene therapy through activation of the CMV promoter in pancreatic cancer cells.

Adenovirus-mediated gene therapy shows remarkable promise as a new strategy for advanced pancreatic cancer, but satisfactory clinical results have not yet been obtained. To improve this gene therapy, we investigated the effects of gemcitabine (GEM) on transgene expression by adenoviral vectors and their biological effects. We used Ad-lacZ and adenoviral vector-expressing NK4 (Ad-NK4) as representative adenoviral vectors. These vectors express beta-galactosidase (beta-gal) and NK4 (which inhibits the invasion of cancer cells), respectively, under the control of the CMV promoter. Cells were infected with the individual adenoviruses and then treated with GEM. GEM increased beta-gal mRNA expression and beta-gal activity, and increased NK4 expression in both culture media and within infected cells, in dose-dependent manners. The increased expression of NK4 delivered by Ad-NK4 had biological effects by inhibiting the invasion of cancer cells. GEM also enhanced NK4 expression in SUIT-2 cells transfected with an NK4-expressing plasmid, suggesting that GEM enhanced CMV promoter activity. In in vivo experiments, NK4 expression within subcutaneously implanted tumors was increased in GEM-treated mice compared with control mice. These results suggest that adenovirus-mediated gene therapy with GEM may be a promising approach for treating pancreatic cancer, and that this combination therapy may decrease the risks of side effects.

Pleiotropic effects of mitiglinide in type 2 diabetes mellitus.

This study investigated the effects of mitiglinide in 16 patients with type 2 diabetes mellitus treated with 30 mg/day mitiglinide, divided into three doses given just before each meal, for approximately 12 months. A 450 kcal meal tolerance test was performed at baseline and after 3, 6 and 12 months, and levels of plasma glucose and immunoreactive insulin were measured. Various parameters of glucose metabolism and lipid metabolism, urinary albumin and markers of atherosclerosis, coagulation and fibrinolysis were also determined. Mitiglinide showed a rapid stimulatory effect on insulin secretion and reduced the levels of plasma glucose. The free fatty acid level significantly decreased at 60 min after the meal tolerance test. Mitiglinide also significantly lowered glycosylated haemoglobin and raised 1,5-anhydroglucitol after 6 months, and significantly decreased urinary albumin after 12 months. These data indicate that mitiglinide may have beneficial effects not only on glycaemic control but also on lipid metabolism and urinary albumin excretion, and may have a role in the prevention of the vascular complications of diabetes.

Over-expression of S100A2 in pancreatic cancer correlates with progression and poor prognosis.

Controversy exists regarding the clinical significance of S100A2 in the progression of tumours. In pancreatic cancer, little is known about the role of S100A2. The aim of this study was to clarify the clinical significance of S100A2 expression in pancreatic carcinogenesis. We microdissected invasive ductal carcinoma (IDC) cells from 22 lesions, pancreatic intraepithelial neoplasia (PanIN) cells from five lesions, intraductal papillary mucinous neoplasm (IPMN) cells from 38 lesions, pancreatitis-affected epithelial (PAE) cells from 16 lesions, and normal ductal cells from 18 normal pancreatic tissues. S100A2 expression in 14 pancreatic cancer cell lines, microdissected cells and formalin-fixed paraffin-embedded (FFPE) samples was examined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Microdissection analyses revealed that IDC cells expressed higher levels of S100A2 than did IPMN, PAE or normal cells (all comparisons, p < 0.007). Cell lines from metastatic sites expressed higher levels of S100A2 than those from primary sites. PanIN cells expressed higher levels of S100A2 than normal cells (p = 0.018). IDC cells associated with poorly differentiated adenocarcinoma expressed higher levels of S100A2 than did IDC cells without poorly differentiated adenocarcinoma (p = 0.006). Analyses of FFPE samples revealed that levels of S100A2 were higher in samples from patients who survived < 1000 days after surgery than in those from patients who survived > 1000 days (p = 0.043). Immunohistochemical analysis was consistent with qRT-PCR. S100A2 may be a marker of tumour progression or prognosis in pancreatic carcinogenesis and pancreatic cancer.

Sonic hedgehog is an early developmental marker of intraductal papillary mucinous neoplasms: clinical implications of mRNA levels in pancreatic juice.

Intraductal papillary mucinous neoplasms (IPMNs) are common cystic tumours of the pancreas. Sonic hedgehog (SHH) is involved in gastric epithelial differentiation and pancreatic carcinogenesis. However, a comprehensive analysis of SHH expression in IPMN has not yet been performed. In the present study, one-step quantitative real-time reverse transcription-polymerase chain reaction with gene-specific priming was used to examine mRNA levels in various types of clinical samples. SHH expression in IPMN was measured and the possible association of gastric epithelial differentiation with development of IPMN was evaluated. In bulk tissue analyses (IPMNs, 11 pancreatic cancer, and 20 normal pancreatic tissues), IPMN expressed significantly higher levels of SHH than did normal pancreas (IPMN versus normal pancreas, p = 0.0025; pancreatic cancer versus normal pancreas, p = 0.0132), but SHH expression did not differ between IPMN and pancreatic cancer (p = 0.3409). In microdissection analyses (infiltrating ductal carcinoma cells from 20 sections, IPMN cells from 20 sections, pancreatitis-affected epithelial cells from 11 sections, and normal epithelial cells from 12 sections), IPMN cells expressed significantly higher levels of SHH than did cancer cells, normal cells, or pancreatitis-affected ductal cells (all comparisons, p < 0.008). Pancreatic juice analyses (20 samples from pancreatic cancers, 31 samples from IPMNs, and 27 samples from chronic pancreatitis) revealed that SHH expression differed significantly between IPMN juice and pancreatitis juice (p < 0.0001), and between cancer juice and pancreatitis juice (p = 0.0125). Receiver operating characteristic curve analyses revealed that SHH measurement in pancreatic juice was useful for discriminating IPMN from chronic pancreatitis (area under the curve = 0.915; 95% confidence interval: 0.796-0.976). The data suggest that overexpression of SHH is an early event in the development of IPMN and that SHH measurement in pancreatic juice may provide some advantages for the treatment or follow-up of a subset of patients with IPMN or chronic pancreatitis.

Optimal antidiarrhea treatment for antitumor agent irinotecan hydrochloride (CPT-11)-induced delayed diarrhea.

PURPOSE: An antitumor camptothecin derivative CPT-11 has proven a broad spectrum of solid tumor malignancy, but its severe diarrhea has often limited its more widespread use. We have demonstrated from a rat model that intestinal beta-glucuronidase may play a key role in the development of CPT-11-induced delayed diarrhea by the deconjugation of the luminal SN-38 glucuronide, and the elimination of the intestinal microflora by antibiotics or dosing of TJ-14, a Kampo medicine that contains beta-glucuronidase inhibitor baicalin, exerted a protective effect. In the present study, we assessed the efficacy of several potential treatments in our rat model to clarify which is the most promising treatment for CPT-11-induced delayed diarrhea. METHODS AND RESULTS: Oral dosing (twice daily from days -1 to 4) of streptomycin 20 mg/kg and penicillin 10 mg/kg (Str/Pen), neomycin 20 mg/kg and bacitracin 10 mg/kg (Neo/Bac), both of which inhibited almost completely the fecal beta-glucuronidase activity, or TJ-14 1,000 mg/kg improved the decrease in body weight and the delayed diarrhea symptoms induced by CPT-11 (60 mg/kg i.v. from days 1 to 4) to a similar extent. The efficacy was less but significant in activated charcoal (1,000 mg/kg p.o. twice daily from days -1 to 4). In a separate experiment using rats bearing breast cancer (Walker 256-TC), TJ-14, Neo/Bac, and charcoal at the same dose regimen improved CPT-11-induced intestinal toxicity without reducing CPT-11's antitumor activity. In contrast, oral dosing (twice a day) of cyclosporin A (50 mg/kg), a P-glycoprotein and cMOAT/MRP2 inhibitor or valproic acid (200 mg/kg), a UDP-glucuronosyltranferase inhibitor, exacerbated the intestinal toxicity without modifying CPT-11's antitumor activity. CONCLUSIONS: The result clearly demonstrated the ability of Neo/Bac, Str/Pen, and TJ-14, less but significant ability of activated charcoal, to ameliorate CPT-11-induced delayed-onset diarrhea, suggesting the treatments decreasing the exposure of the intestines to the luminal SN-38 are valuable for improvement of CPT-11-induced intestinal toxicity. In contrast, the treatments affecting the biliary excretion of CPT-11 and its metabolites might have undesirable results.

Peritumoral injection of adenovirus vector expressing NK4 combined with gemcitabine treatment suppresses growth and metastasis of human pancreatic cancer cells implanted orthotopically in nude mice and prolongs survival.

NK4 or adenovirus vector expressing NK4 (Ad-NK4) can act bifunctionally as a hepatocyte growth factor antagonist and angiogenesis inhibitor and has potential value in cancer therapy. The aim of this study was to evaluate the therapeutic efficacy of Ad-NK4 in combination with gemcitabine (GEM) against pancreatic cancer. In vitro study showed a strong antiproliferative effect of GEM and a potent anti-invasive effect of Ad-NK4 against pancreatic cancer cells. In in vivo experiments, SUIT-2 human pancreatic cancer cells were implanted into the pancreas of nude mice. Mice were treated with Ad-NK4 by injection into the peritumoral region of the pancreas on day 5 after implantation followed by weekly i.p. injections of GEM. On day 28 after implantation, pancreatic tumor volume was significantly smaller than that in mice treated with Ad-LacZ, Ad-NK4 alone, or GEM alone. Furthermore, combination therapy completely suppressed peritoneal dissemination and liver metastases, leading to significantly increased survival. Histologic and immunohistochemical assays of primary tumors indicated that combination therapy prohibited both cell proliferation and angiogenesis, resulting in high levels of apoptosis. These results suggest that peritumoral injection of Ad-NK4 plus GEM is a potent combination therapy for pancreatic cancer.

Laparoscopically assisted distal gastrectomy with standard radical lymph node dissection for gastric cancer.

BACKGROUND: Laparoscopically assisted distal gastrectomy (LADG) with limited lymph node dissection (D1+alpha) has been used to treat a subset of patients with early gastric cancer. Technical advances have expanded indications for LADG to more advanced gastric cancers. However, little data are available on the feasibility or advantages of LADG with standard radical D2 lymph node dissection for patients with gastric cancer. METHODS: This study reviewed the clinical features of 37 patients who underwent LADG with D2 lymph node dissection for preoperatively diagnosed gastric carcinoma, then compared the results with the features of 31 patients who underwent conventional open distal gastrectomy (ODG) with D2 lymph node dissection. RESULTS: The laparoscopic procedure was not converted to laparotomy in any patient. There was no operative mortality and no serious morbidity among the patients who underwent LADG with D2 lymph node dissection. As compared with the ODG group, the LADG group had less operative blood loss (p < 0.001), earlier recovery of bowel activity (p = 0.012), and a shorter duration of fever after surgery (p = 0.015), despite the longer operation time (p = 0.007). CONCLUSIONS: According to this study, LADG with D2 lymph node dissection is feasible and provides several advantages similar to those of limited lymph node dissection (D1+alpha). Depending on surgeons' technical proficiency, LADG can be used with standard radical lymph node dissection for patients with gastric cancers.

Laparoscopic wedge resection of gastric submucosal tumors.

BACKGROUND/AIMS: The purpose of this study was to evaluate the clinical utility of laparoscopic surgery for gastric submucosal tumor. METHODS: The records of 11 patients who underwent laparoscopic wedge resection (LR group) for gastric submucosal tumors were reviewed and compared with those of 8 patients who underwent open surgery (OS group). RESULTS: Mean operation time was 145 +/- 43 min in the LR group and 127 +/- 33 min in the OS group (p = 0.301). Mean blood loss was 97 +/- 107 and 107 +/- 47 g, respectively (p = 0.387). Patients in the LR group began walking 1.4 +/- 0.7 days after surgery, which was significantly earlier than those in the OS group (2.7 +/- 1.3 days, p = 0.021). The first flatus (1.5 +/- 0.5 vs. 3.1 +/- 0.6 days, respectively, p = 0.0004) and resumption of oral food intake (3.0 +/- 1.7 vs. 4.3 +/- 0.9 days, respectively, p = 0.020) were also earlier in the LR group. White blood cell count on the first postoperative day was lower (7,000 +/- 2,100 vs. 11,900 +/- 3,580/mm(3), respectively, p = 0.004) in the LR group than in the OS group, and the duration of fever (>38.0 degrees C; 0.1 +/- 0.3 vs. 0.9 +/- 0.8 days, respectively, p = 0.014) and the period of postoperative hospitalization (13.2 +/- 3.7 vs. 20.8 +/- 6.1 days, respectively, p = 0.014) were significantly shorter in the LR group than in the OS group. No complications occurred in either group. CONCLUSION: Laparoscopic surgery was superior to open surgery in terms of postoperative recovery time with comparable operation time and blood loss. Laparoscopic wedge resection is a promising surgical alternative for the treatment of gastric submucosal tumors.

Involvement of bone morphogenic protein-2 (BMP-2) in the pathological ossification process of the spinal ligament.

OBJECTIVE: To investigate the function of bone morphogenic protein-2 (BMP-2) in the ossification of the spinal ligament (OSL). METHODS: Total RNA was prepared from the cultured spinal ligament cells from patients with OSL and analysed by reverse transcription-polymerase chain reaction using specific primers for BMP-2. BMP-2 mRNA expression in ligament tissues was examined by in situ hybridization. Spinal ligament cells from patients without OSL were treated with BMP-2 and examined for alkaline phosphatase activity. RESULTS: Expression of the BMP-2 gene was detected in cultured spinal ligament cells. In ligament tissues, BMP-2 mRNA was present in the chondrocyte-like cells in the fibrocartilage zone. Exogenous BMP-2 increased alkaline phosphatase activity in spinal ligament cells from patients without OSL. CONCLUSION: The BMP-2 gene is expressed in the spinal ligaments of OSL patients, and exogenous BMP-2 stimulates osteogenic differentiation of spinal ligament cells. The expression of BMP-2 in the spinal ligaments could be a clue in elucidating how heterotrophic osteogenesis develops in ligament tissue.

Pancreatoduodenectomy for pancreatic head carcinoma with or without pylorus preservation.

BACKGROUND/AIMS: With the concept of less invasive surgery, PpPD (pylorus-preserving pancreatoduodenectomy) has taken the place of conventional Whipple pancreatoduodenectomy (Whipple) as a standard operation for pancreatic head carcinoma. The aim of this paper is to compare early and late postoperative results of PpPD and Whipple for pancreatic head carcinoma. METHODOLOGY: Postoperative clinical follow-up data and outcome of 50 Japanese patients with pancreatic head carcinoma who underwent pancreatoduodenectomy with or without pylorus preservation were reviewed to scrutinize the demerits and merits of the pylorus preservation. RESULTS: Preoperative and postoperative serum chemistry was not different between the two groups. Mean operation time of the Whipple group was 517 minutes, which was significantly shorter than 624 minutes of the PpPD group (P = 0.0006). Cumulative stage was not different between the two groups. Cumulative curability of the PpPD group was superior to the Whipple group; of the 27 patients with Whipple, A in 4, B in 5 and C in 18, while of the 23 patients with PpPD, A in 12, B in 2 and C in 9 (P = 0.0182). Gastric tube was removed on POD 6.0 in the Whipple group, while on POD 39 in the PpPD group (P < 0.0001). Oral intake was started on POD 14.0 in the Whipple group, while on POD 28.3 in the PpPD group (P = 0.0018). Discharge was on POD 57.8 in the Whipple group, while POD 86.9 in the PpPD group (P = 0.0023). At the time of discharge and postoperative 6, 12, and 18 months, body weight loss from the preoperative level was 1kg smaller in the PpPD group than in the Whipple group. 1-year and 3-year survival rates of the Whipple group was 53.8% and 15.8%, while 62.8% and 19.6% of the PpPD group, showing no significant difference. CONCLUSIONS: These data show that delayed gastric emptying is evident in the PpPD group, resulting in longer hospital stay, while long-term body weight loss is smaller in this group. The clinical outcome is similar between the two groups. PpPD can be accepted as a standard operation for pancreatic head carcinoma.

Benign pseudotumorous lesion (fibroangiomyomatous hyperplasia with elastosis) in the gallbladder.

We describe a rare case of a benign pseudotumorous lesion (fibroangiomyomatous hyperplasia with elastosis) in the gallbladder in a 44-year-old Japanese woman, and discuss the rarity of elastosis in the gallbladder. To our knowledge, this case may be the first report of a pseudotumorous lesion of the gallbladder with elastosis in Japan.

Stepwise progression of centrosome defects associated with local tumor growth and metastatic process of human pancreatic carcinoma cells transplanted orthotopically into nude mice.

Recent evidence indicates that loss of centrosome integrity may be a major cause of genetic instability underlying various human cancers. The aim of this study was to define the role of centrosome defects during the in vivo tumor progression of pancreatic carcinoma using an orthotopic implantation model. Injection of Suit-2 human pancreatic cancer cells into the pancreata of nude mice reproduced the pattern of local tumor growth and distant metastasis observed in humans. Pancreatic xenografts, peritoneal disseminations, and hepatic metastases were harvested, and tumor cells were examined for centrosomes by immunofluorescence microscopy. Centrosome abnormalities, characterized by increased numbers of centrosomes, were detected in only a small fraction of parental Suit-2 cells in culture, whereas the frequency was markedly increased in cells isolated from the pancreatic xenografts. Abnormal centrosome numbers were found at higher frequencies in metastatic foci than in pancreatic xenografts. A significant positive correlation existed between the fraction of cells with multiple centrosomes and that with multipolar mitotic spindles, suggesting a functional involvement of aberrant centrosomes in spindle disorganization and chromosome missegregation. In addition, the increased frequency of abnormal centrosomes was associated with an enhanced degree of chromosomal instability. These findings suggest a novel model of pancreatic tumor progression whereby a stepwise increase in the magnitude of centrosomal abnormalities confers an increased chance for aberrant mitotic events, thus accelerating genetic instability and causing the tumor to progress to a more advanced stage.

Effect of serum depletion on centrosome overduplication and death of human pancreatic cancer cells after exposure to radiation.

The tumor microenvironment is one of the key factors affecting the cellular response to radiation; however, the influence of serum concentration on tumor radiosensitivity remains poorly understood. We recently discovered that gamma-irradiation of tumor cells causes centrosome overduplication, which may lead to lethal nuclear fragmentation through the establishment of multipolar mitotic spindles. In the present study, we investigated the effect of serum depletion on radiation-induced cell death in relation to the centrosome dynamics in human pancreatic cancer cells. Exposure of Capan-1 cells to gamma-irradiation resulted in a time-dependent increase in cells containing multiple centrosomes in association with the appearance of mitotic cell death. Treatment of irradiated cells with serum depletion drastically accelerated centrosome overduplication and the formation of multipolar spindles, resulting in increased nuclear fragmentation and cell death. Cell cycle analysis of irradiated cultures revealed that the reduced serum level increased the population of cells arrested in the G2/M phase, which might be responsible for the abnormal centrosome accumulation. These findings suggest that serum concentration can influence radiation-induced cell killing through modulating cell cycle progression and possibly centrosome overduplication.

Quantitative analysis of hTERT mRNA expression in colorectal cancer.

OBJECTIVES: Telomerase is highly activated in a variety of malignant neoplasms including colon cancer. Among the major components of telomerase, human telomerase reverse transcriptase (hTERT) is thought to regulate telomerase activity. To assess the importance of telomerase for the diagnosis of colorectal cancer, we measured the expression of hTERT mRNA and telomerase activity in a large series of 140 colorectal cancers, 140 adjacent normal tissues, and 20 adenomas. METHODS: The expression level of hTERT was measured quantitatively by competitive reverse transcriptase-polymerase chain reaction (RT-PCR), and telomerase activity was examined by telomeric repeat amplification protocol (TRAP) assay in the same samples. RESULTS: The median expression level of hTERT mRNA in carcinomas was significantly higher than that in either adenomas or normal tissues. The median level of hTERT in adenomas was significantly higher than that in normal tissues. Telomerase activities in carcinomas were significantly higher than those in either adenomas or normal tissues. Telomerase activities in adenomas were also significantly higher than those in normal tissues. Furthermore, the relative expression levels of hTERT mRNA in adenomas and carcinomas were significantly correlated with the relative telomerase activities; the Spearman rank correlation was 0.53 (p = 0.021) and 0.18 (p = 0.031), respectively. CONCLUSIONS: Our data suggest that determination of hTERT mRNA by competitive RT-PCR is superior in quantitative accuracy and sensitivity and would support the importance of telomerase activity for the diagnosis of colorectal cancer.

Repair of denture base resin using woven metal and glass fiber: effect of methylene chloride pretreatment.

STATEMENT OF PROBLEM: A durable repairing system for denture base fracture is desired to avoid recurrent fracture. Purpose. This study evaluated the strength and modulus of elasticity of repaired acrylic specimens reinforced with various processes. MATERIAL AND METHODS: Transverse strength and modulus of elasticity of repaired acrylic denture base specimens were evaluated with a 3-point bending test and compared with a heat-polymerized control. Autopolymerizing acrylic resin was used with woven metal fiber and glass fiber with and without methylene chloride surface treatment (n = 6 per group). The specimens were cut in half and fixed in a metal mold to obtain a space for placing the repairing resin. A cavity was prepared when metal or glass fiber was used. All specimens were stored in 37 degrees C distilled water for 48 hours before the test. All data were statistically analyzed with 1-way ANOVA, and differences among groups were analyzed with Fisher test (P< or =.05). RESULTS: The mean value of the transverse strength for the control was 87.2 MPa. The specimens repaired by glass fiber with methylene chloride surface treatment exhibited the highest transverse strength (96.8 MPa), which was significantly higher than that of the control (P< or =.05). The elastic modulus of the specimens repaired by glass fiber with methylene chloride surface treatment (4189.3 MPa) was significantly greater than that of the control (2683.7 MPa) at a 95% level of confidence. The values of transverse strength and elastic modulus were highest when the surface treatment was combined with a reinforcing glass fiber. CONCLUSION: Reinforcement with glass fiber and methylene chloride pretreatment produced transverse strength and a modulus of elasticity higher than the control.

Correlation between centrosome abnormalities and chromosomal instability in human pancreatic cancer cells.

Chromosomal instability, characterized by abnormal numbers or structures of chromosomes, is a common feature of human cancers, but the mechanisms behind these changes are still unclear. Since centrosomes play a pivotal role in balanced chromosomal segregation during mitosis, we attempted to investigate the association between centrosome abnormalities and chromosomal instability in a large number of human pancreatic cancer cell lines. Immunofluorescence microscopy revealed centrosomes that were highly atypical with respect to their size, shape, and number in most cell lines. These abnormal centrosomes contributed to the assembly of multipolar spindles, resulting in defective mitosis and chromosome mis-segregation. Interestingly, a high frequency of centrosome defects inversely correlated with the growth rate of cells in culture. Fluorescence in situ hybridization revealed a dramatic variation of chromosome numbers in cell lines with the defective centrosome phenotype. Furthermore, a significant positive correlation existed between the level of centrosome defects and the level of chromosomal imbalances. These results indicate that centrosome abnormalities can lead to spindle disorganization and chromosome segregation errors, which may drive the accumulation of chromosomal alterations. Thus, defects in centrosome function may be an underlying cause of genetic instability in human pancreatic cancers.

Surgical treatment of patients with T2 gallbladder carcinoma invading the subserosal layer.

BACKGROUND: Because T2 carcinoma of the gallbladder that invades perimuscular connective tissue without extension beyond serosa or into the liver has a hope for longterm survival, we attempted to clarify significant prognostic factors with respect to tumor- and surgery-related variables. STUDY DESIGN: Of 65 patients with gallbladder carcinoma who had undergone surgical resection from 1983 to 1999, 28 had T2 carcinoma histologically proved. The significance of variables for survival was examined by the Kaplan-Meier method and log-rank test followed by multivariate analyses using Cox's proportional hazard model. RESULTS: There were 17 patients with stage II carcinoma (T2 N0 M0), 6 with stage III (T2 N1 M0), and 5 with stage IVB. Lymph node metastasis was present in 11 patients (39%) and it reached to the peripancreatic head region (N2) in 5 of them. Lymphatic, venous, and perineural invasions were found in 68%, 57%, and 43%, respectively. With respect to tumor factors, the absence of perineural invasion (Odds ratio [OR] 16.77, 95% confidence interval [CI] 2.17-129.94, p = 0.0069), absence of lymph node metastasis (OR 15.00, 95% CI 2.08-108.33, p = 0.0073), and stage II (II versus III and IVB, OR 15.00, 95% CI 2.08-108.33, p = 0.0073) were significant factors related to good postoperative survival in the multivariate analysis. Surgical procedure (radical resection versus cholecystectomy, OR 4.31, 95% CI 1.34-13.82, p = 0.0142) and surgical margin (OR 7.41, 95% CI 2.19-25.13, p = 0.0013) were significant factors in the univariate analysis. Cancer-free surgical margins provided a significantly better survival (5-year survival rate, 62%); none with cancer-positive surgical margins survived for more than 27 months. In the multivariate analysis, surgical procedure was significant (OR 25.49, 95% CI 1.62-400.72, p = 0.021). Radical surgery, including extended cholecystectomy (resection of the gallbladder together with the gallbladder bed of the liver) and anatomic resection of liver segment 5 and of the lower part of segment 4, gave a significantly better 5-year survival rate than cholecystectomy (59% versus 17%). The 5-year survival rate after radical resection in patients with stage II was 75%; that in patients with stage III and IVB was 33%. CONCLUSIONS: Results suggest that radical surgery is the treatment of choice for patients with T2 carcinoma of the gallbladder. The presence of lymph node metastasis, perineural invasion, or both suggests the necessity of additional treatment after radical surgery.

Possible role of telomerase activation in the multistep tumor progression of periampullary lesions in patients with familial adenomatous polyposis.

OBJECTIVES: The role of telomerase in periampullary tumor progression in patients with familial adenomatous polyposis (FAP) was investigated. METHODS: Relative telomerase activity was measured using a telomerease amplification protocol in periampullary biopsy specimens of normal mucosa and adenoma obtained from patients with FAP, and was compared with that of periampullary normal mucosa and cancer specimens from patients without FAP. RESULTS: None of normal mucosa from the non-FAP patients showed a telomerase ladder. Telomerase was positively detected in three of seven normal mucosa (42.9%) and in five of seven adenoma from FAP patients (62.5%). In papillary cancer from the non-FAP patients, seven of nine tissue specimens (77.8%) showed positive activity. When semiquantitatively analyzed, the relative telomerase activity increased in accordance with the progression of the diseases. CONCLUSIONS: Telomerase is activated even in normal mucosa of FAP patients, and the intensities of telomerase may reflect the malignant potential of periampullary neoplasms.