Nobuyasu Takada

A comparison of video-assisted thoracoscopic oesophagectomy and radical lymph node dissection for squamous cell cancer of the oesophagus with open operation.

An Erratum has been published for this article in British Journal of Surgery 90(6) 2003, 764.

Cancer prevention by organosulfur compounds from garlic and onion

Environmental compounds are known to be involved in both the generation and prevention of many human cancers. It is important to discover naturally occurring or synthetic compounds which can block the process of carcinogenesis. We have focused attention on several organosulfur compounds (OSCs) in garlic and onion, and analyzed their potential for chemoprevention in the post‐initiation stage in a liver medium‐term bioassay (Ito test) and a multi‐organ carcinogenesis bioassay. In the ITO test, rats were given diethylnitrosamine (DEN), 200 mg/kg b.w., i.p.; starting 2 weeks later they were treated with test chemicals for 6 weeks and then killed. All rats were subjected to 2/3 hepatectomy 1 week after the start of test chemical treatment. Inhibitory effects of a number of compounds could be identified in terms of reduced numbers and areas of liver glutathione S‐transferase placental (GST‐P) positive foci. In the multi‐organ carcinogenesis bioassay, rats were given DEN, N‐methyl‐N‐nitrosourea, N‐butyl‐N‐(4‐hydroxybutyl)nitrosamine, N, N′‐dimethylhydrazine, and dihydroxy‐dipropylnitrosamine during the first 4 weeks, followed by test chemicals for 24 weeks. Various organs were examined. As a result, oil‐soluble OSCs such as methyl propyl disulfide and propylene sulfide demonstrated inhibitory effects on the development of GST‐P positive foci. Moreover, water‐soluble OSCs such as S‐methylcysteine and cysteine similarly decreased GST‐P focus formation. In contrast, OSCs such as diallyl sulfide, diallyl trisulfide, and allyl methyl trisulfide enhanced formation of such altered hepatocellular foci. Inhibitory potential for colon and renal carcinogenesis was observed in rats treated with diallyl disulfide. Thus, the results indicate that some OSCs exert chemopreventive effects on chemical carcinogenesis. It must, however, be borne in mind that they may also demonstrate promotion potential, depending on the organ examined. J. Cell. Biochem. Suppl. 27:100–105.

Learning curve of video-assisted thoracoscopic esophagectomy and extensive lymphadenectomy for squamous cell cancer of the thoracic esophagus and results

Background: The efficacy of thoracoscopic radical esophagectomy for cancer of the thoracic esophagus and the learning curve required have yet to be clearly established. Methods: Eighty treatment-naive patients with esophageal cancer without contiguous spread underwent esophageal mobilization and extensive mediastinal lymphadenectomy through a 5-cm minithoracotomy and four trocar ports. The outcomes in the first 34 patients (group 1) and the last 46 patients (group 2) were compared. Results: There were no differences in background or clinicopathologic factors between the two groups. The duration of the thoracoscopic procedure and blood loss were less (p <0.0001), the incidence of postoperative pulmonary infection was less (p = 0.0127), and the number of mediastinal nodes retrieved was greater (p = 0.0076) in group 2. Multivariate analysis demonstrated that surgical experience (number of cases performed) predicted the risk of pulmonary infection (p = 0.0331). Conclusion: Video-assisted thoracoscopic radical esophagectomy can be performed with safety and efficacy comparable to those of open esophagectomy. Morbidity decreases with the surgeons experience.

Prognostic significance of the MIB‐1 proliferation index for patients with squamous cell carcinoma of the esophagus

Background. A number of studies have indicated that the ki‐67 proliferation index is of important prognostic significance for a variety of neoplasias. It was the aim of this study to investigate whether any correlation exits between the MIB‐1 proliferation index and various clinicopathologic parameters in squamous cell carcinomas of the esophagus from 72 patients (20 women: median age, 64 years; range, 45–79 years; and 52 men: median age, 61 years; range, 43–77 years).

Reconstructive Procedure after Distal Gastrectomy for Gastric Cancer that Best Prevents Duodenogastroesophageal Reflux

Billroth I and II reconstructions are commonly performed after distal gastrectomy. Both may cause duodenogastric and duodenogastro-esophageal reflux, conditions reported to have carcinogenetic potential. The aim of this study was to investigate which reconstructive procedure would most effectively prevent bile reflux into the gastric remnant and esophagus after distal gastrectomy. A group of 92 patients who underwent curative distal gastrectomy for gastric cancer were subjected and classified into three groups retrospectively by the reconstructive procedure undertaken: group A, Roux-en-Y (Roux-Y) reconstruction (n=29); group B, Billroth I reconstruction (n=41); group C, Billroth II reconstruction (n=22). The bile reflux periods (percent time) for the gastric remnant and esophagus were measured with the Bilitec 2000 under standardized conditions. The percent time for the gastric remnant was significantly less in group A than in group B or C. In 61% of all patients, bile reflux into the esophagus was found to be more than 5.0% of the time; it was less in group A than in group B or C (p=0.057). A questionnaire revealed a good correlation between the incidence of reflux symptoms and the percent time for the gastric remnant and esophagus. Roux-Y reconstruction is superior to either Billroth I or II reconstruction for preventing bile reflux into the gastric remnant and esophagus after distal gastrectomy.RésuméLe rétablissement de continuité après gastrectomie distale est habituellement selon Billroth I ou selon Billroth II. Cependant, les deux types de reconstruction peuvent être responsables de reflux duodénogastrique et de reflux duodénogastroesophagien, avec un risque plus élevé de développer un cancer. Le but de cette étude a été de déterminer quel type de rétablissement serait le plus efficient dans la prévention du reflux de bile dans le moignon gastrique et dans l’œsophage après gastrectomie distale. Quatre-vingt-deux patients qui ont eu une gastrectomie distale à visée curatrice pour cancer ont été inclus et classés rétrospectivement en trois groupes selon le type de reconstruction: groupe A, reconstruction par anse en Y (n=29); groupe B, rétablissement de continuité selon Billroth I (n=41); et groupe C, rétablissement selon Billroth II (n=22). La durée du reflux (en pourcentage de temps) au niveau du moignon gastrique et de l’œsophage a été mesurée dans des conditions standardisées Bilitec 2000. Le pourcentage de temps pour le moignon gastrique a été signifieativement plus bas dans le groupe A que dans les groupes B et C. La durée du reflux de bile dans l’œsophage a dépassé 5% chez 61% des patients: elle a été moins longue dans le groupe I que dans les groupes B et C (p=0.057). Grâce à un questionnaire on a pu trouver une bonne corrélation entre l’incidence des symptômes de reflux et la durée du temps de reflux dans le moignon gastrique et dans l’œsophage. Le rétablissement de continuité par anse en Y est supérieur aux rétablissements de types Billroth I et II en ce qui concerne la prévention de reflux de bile dans le moignon gastrique et dans l’œsophage après gastrectomie distale.ResumenLas reconstrucciones tipos Billroth I y II son las más comunes cuando se practica una gastrectomía. Sin embargo, ambas pueden causar reflujo duodenogástrico y duodeno gastroesofágico, fenómeno que se reconocen como de potencial efecto carcinogenético. El propósito del presente estudio fue investigar cuál procedimiento de reconstrucción podría prevenir el reflujo al remanente gástrico y al esófago luego de una gastrectomía distal. Noventa y dos pacientes sometidos a gastrectomía distal curativa por cáncer fueron clasificados retrospectivamente en 3 grupos: grupo A, reconstrucción de Roux-en-Y (n=29); grupo B, reconstrucción Billroth I (n=41); grupo C, reconstrucción Billroth II (n=22). El periodo de reflujo biliar (por ciento del tiempo) al estómago residual y al esófago fue determinado mediante Bilitec 2000 bajo condiciones estandarizadas. El porcentaje de tiempo para el estómago residual fue significativamente menor en el grupo A en comparación con los grupos B y C. En 61% de la totalidad de los pacientes se encontró reflujo al esófago por más del 5% del tiempo; fue menor en el grupo A que en los grupos B y C (p=0.057). La aplicación de un cuestionario reveló buena correlación entre la incidencia de los síntomas de reflujo y el porcentaje de tiempo del reflujo al remanente gástrico y al esófago. La reconstrucción de Roux-en-Y es superior a las reconstrucciones Billroth I y II en cuanto a la prevención del reflujo biliar al remanente gástrico y al esófago luego de una gastrectomía distal.

Comparison of three-field esophagectomy for esophageal cancer incorporating open or thoracoscopic thoracotomy.

Background: Thoracoscopic esophagectomy for esophageal cancer has been performed as an alternative to open surgery to reduce surgical trauma. However, its effect on pulmonary function, exercise tolerability, and quality of life is unknown. Methods: Fifty-one patients with esophageal cancer underwent thoracic esophagectomy with radical lymphadenectomy by posterolateral thoracotomy (29 cases) or thoracoscopic surgery (22 cases). Patients performed spirometry and exercise tolerance testing and completed a quality-of-life questionnaire before and 3 months after surgery. Results: Pre-to-postoperative change in vital capacity was 74.3 ± 10.6% in the thoracotomy group and 84.9 ± 10.4% in the thoracoscopy group (p = 0.021). Maximum oxygen uptake was similar, but dyspnea was the more common factor limiting exercise tolerance postoperatively in the thoracotomy group. Change in pre-to-postoperative performance status was 1.20 ± 0.62 in the thoracotomy group and 0.55 ± 0.51 in the thoracoscopy group (p = 0.0003). Conclusions: Thoracoscopic esophagectomy for esophageal cancer has better preservation of pulmonary function and quality-of-life.

Video-assisted thoracoscopic esophagectomy and radical lymph node dissection for esophageal cancer: A series of 75 cases

AbstractsBackground: The efficacy of thoracoscopic radical esophagectomy for cancer has yet to be established, mainly because previous reports have not included a sufficient number of cases. Methods: Seventy-five treatment-naive patients with esophageal cancer without contiguous spread underwent esophageal mobilization and extensive mediastinal lymphadenectomy through a 5-cm mini-thoracotomy and four trocar ports. Results: Video-assisted thoracoscopic surgery was performed without major intraoperative complications or emergency conversion to open surgery. We retrieved 34.1±13.0 mediastinal nodes, including 11.5±3.8 tracheobronchial nodes and 6.2±3.0 recurrent laryngeal nodes. Mean time of operation and blood loss were less in the last 39 patients than the first 36 (186.7±25.3 min and 165.4±101.8 g vs 270. 2±96.0 min and 421.5±31.2 g, respectively: p <0.0001 and p <0.001). Pulmonary morbidity was 5% in the later 39 patients. Survival was 90%, 80%, and 57% at 1, 2, and 5 years after surgery. Conclusion: Thoracoscopic radical esophagectomy has less morbidity and comparable survival to conventional surgery, after a moderate amount of experience. Mini-thoracotomy is essential to perform the procedure safely and effectively.

Expression of immunoreactive human hepatocyte growth factor in human esophageal squamous cell carcinomas

Hepatocyte growth factor (HGF) is a potent mitogen for epithelial cells that promotes cell motility and invasiveness. In this study, we report that the human esophageal squamous cell carcinoma (SCC) shows a significant elevation of HGF concentration (600 +/- 416 ng/100 mg protein), compared to normal mucosa (80 +/- 183 ng/100 mg protein) (P < 0.01). An association could be established between levels of HGF and decreasing differentiation of 37 SCCs. The 2-year crude survival rates were 51.1% and 68.4% at high and low HGF concentrations, respectively. The results indicate that HGF is significantly increased in human esophageal SCCs, especially of poorly differentiated type. HGF might thus be useful as a biological biomarker for characterization of human esophageal SCCs.

S-Methylcysteine and Cysteine Are Inhibitors of Induction of Glutathione S-Transferase Placental Form-positive Foci during Initiation and Promotion Phases of Rat Hepatocarcinogenesis

S‐Methylcysteine (SMC) occurs in a variety of plants, including Allium sativum, Phaseolus vulgaris, and Cruciferae. In this study, we synthesized five organosulfur compounds (OSCs), SMC and four analogs, and examined their modifying effects on diethylnitrosamine‐induced neoplasia of the liver in male F344 rats, using the medium‐term bioassay system of Ito (Ito test) based on the two‐step model of hepatocarcinogenesis. In addition, we investigated the modifying effects of SMC and cysteine on the initiation stage of rat hepatocarcinogenesis. Carcinogenic potential was scored by comparing the numbers and areas of induced glutathione 5‐transferase placental form (GST‐P)‐positive hepatocellular foci. All OSCs examined had a tendency to decrease the number of GST‐P‐positive foci when given in the promotion stage of the Ito test, and in particular SMC and cysteine exerted significant inhibitory effects. When given during the initiation stage, these two OSCs also significantly inhibited focus formation. Regarding the mechanism underlying the inhibitory effects of SMC and cysteine, measurement of ornithine decarboxylase in SMC‐ and cysteine‐treated liver tissues after partial hepatectomy (PH) revealed a significantly reduced activity, and the proportion of hepatocytes positive for proliferating cell nuclear antigen was significantly decreased by SMC or cysteine administration. Moreover, examination of the expression of the early response proto‐oncogenes, c‐fos, c‐jun, and c‐myc, after PH demonstrated down‐regulated induction of c‐jun mRNA transcripts by SMC, sustained for an eight‐hour period. Our results support the view that SMC and cysteine are chemopreven‐tive agents for rat hepatocarcinogenesis and that their intake may he of importance for cancer prevention.

Overexpression of cyclin D1 in rat esophageal carcinogenesis model

Overexpression of cyclin D1 in human esophageal carcinomas has been well documented. The aim of the present study was to assess the expression of cyclin D1 in different types of esophageal epithelial lesions induced by N‐nitrosomethylbenzylamine (NMBA) in rats. A total of 30 rats received s.c.‐injections, five times/week, of 1.0 mg/kg NMBA for a period of 5 weeks followed by the same dose once per week for another 10 weeks. An additional 15 rats were given saline and used as controls to provide normal epithelium. The tumor incidence was 100% at the termination point of 21 weeks. Seventeen rats (57%) showed nuclear staining for cyclin D1, with a great variation in the intensity, as demonstrated by using an immunohistochemical technique. The cyclin D1 positive indices were in the range of 0% to 60% of the individual cells. Negligible staining was observed for normal esophageal epithelium, with a minimal increase in hyperplastic and dysplastic lesions. A significant elevation of cyclin D1 levels was observed in tumors. However, no significant differences were found between papillomas and carcinomas. The immunohistochemical results were confirmed by western blotting analysis. Tumors, papillomas and carcinomas overexpressing cyclin D1 had elevated proliferating cell nuclear antigen (PCNA) indices (P<0.05). The correlation coefficient of overexpressions of PCNA and cyclin D1 was r=0.7 for papillomas, but only r=0.3 for carcinomas. The study thus provides strong evidence of relatively early Overexpression of cyclin D1 during tumorigenesis in the present rat esophageal model. Cyclin D1 expression is not simply a direct consequence of increase cell proliferation.