Chronic reflux esophagitis precedes Barrett's esophagus, which is defined as the columnar-lined epithelium replacing the original squamous epithelial cell lining of the esophagus. Barrett's esophagus carries a risk of malignant transformation to adenocarcinoma. Patients with complicated Barrett's esophagus reflux significantly greater amounts of both acid and duodenal contents than patients with uncomplicated Barrett's esophagus (Vaezi and Richter, 1995). Individuals with a history of gastrectomy often suffer from alkaline reflux esophagitis, and their esophageal carcinoma often develops in the lower third of the esophagus, whereas esophageal carcinoma in patients not subjected to gastrectomy is most frequently located at the middle third of the esophagus (Maeta et al., 1990). Gastric-stump carcinogenesis is associated with duodenogastric reflux. Development of experimental esophageal carcinoma induced by carcinogens is promoted by reflux of duodenal contents (Pera et ab, 1989; Seto et al., 1991; Attwood et al., 1992; Clark et al., 1994) and duodenal contents per se induce rat gastric carcinoma (Miwa ei ai., 199%). This clinical and experimental evidence favors the view that esophageal mucosa may be susceptible to duodenal contents in esophageal carcinogenesis. We have reported that duodenogastric reflux is associated with forestomach and esophageal carcinogenesis in rats (Miwa et al., 1994). However, it is still unresolved which secretions of the refluxate, duodenal or gastric contents, are responsible. In this study we investigate whether reflux of duodenal andtor gastricjuice can cause esophageal carcinogenesis in rats. MATERIAL AND METHODS Experimental animalsWistar male rats weighing approximately 250g were used. They were housed 3 to a cage, and maintained under conditions of 22 2 3°C room temperature and 55 _C 5% humidity with a 12-hr light-dark cycle. They were fed a standard solid chow CRF-1 (Charles River, Japan) and tap water. Surgical proceduresAfter 24 hr fasting, the rats received an upper abdominal incision under diethyl-ether inhalation anesthesia. Then one of the surgical procedures illustrated in Figure 1 was performed on each rat.Gastro-duodeno-esophageal reflux (GDER) (n = 30). After the bilateral vagus nerves were preserved, the abdominal esophagus was transected under the diaphragm, and the distal cut end was closed with sutures. The esophageal stump was anastomosed end-to-side to a loop of jejunum 4 cm distal to Treitz's ligament in an ante-colic manner. This procedure allowed gastro-duodenal contents to flow back into the esophagus.Duodeiio-esophageal reflux (DER) (n = 30). The glandular stomach and forestomach were removed (total gastrectomy), before the duodenal stump was closed with sutures. The esophageal stump was then anastomosed end-to-side to the jejunum approximately 4 cm distal to Treitz's ligament. This surgery induced reflux of duodenal contents into the esophagus.Gastro-esophageal reflu (GER) (n = 30). After the bilateral vagus nerves were preserved, the abdominal esophagus w...

S_mmmmary A study was designed to determine whether oesophageal carcinomas can be induced through reflux of duodenal contents. Male Wistar rats weighing 230 -250 g were divided into three groups according to the surgical procedure performed: (1) the duodenal contents were directed into the forestomach through a stoma (duodeno-forestomach reflux); (2) the duodenal contents were regurgitated into the forestomach through the glandular stomach (duodeno-glandular-forestomach reflux); and (3) a sham operation was performed as a control. Animals were fed standard CRF-1 solid food and tap water that was not exposed to carcinogens and were sacrificed 50 weeks post-operatively. While no neoplasia was observed in any of the 32 control rats, 4/11 (36%) with duodeno-forestomach reflu.x and 3/18 (17%) animals with duodeno-glandular-forestomach reflux developed carcinomas in the lower oesophagus and forestomach. The incidence in each group was significantly higher than in the controls (P<0.01 and P<0.05 respectively). Six of the seven lesions consisted of squamous cell carcinomas, and one was a mucinous adenocarcinoma. Oesophageal columnar epithelial metaplasia was observed in two (18%) of the animals with duodeno-forestomach reflux. Carcinomas were always surrounded by chronic inflammatory changes, including regenerative thickening, basal cell hyperplasia and dysplasia. Additional well-differentiated adenocarcinomas were observed in the prepyloric antrum of 6/18 (33%) animals with duodeno-glandular-forestomach reflux. These findings indicate that chronic reflux of duodenal contents may cause oesophageal carcinoma.Oesophageal adenocarcinoma frequently occurs in the lower oesophagus, in the bed of the columnar-lined epithelium (Barrett's oesophagus) (Naef et al., 1975;McDonald et al., 1977; Witt et al., 1983;Miros et al., 1991). This columnarlined epithelium develops in response to gastro-oesophageal reflux (Mossberg, 1966;Halvorsen & Semp, 1975;Gillen et al., 1988; Seabrook et al., 1992). Thus, the association of adenocarcinoma with gastro-oesophageal reflux is well established. However, there are few data indicating whether squamous cell carcinoma, by far the most frequent type of oesophageal carcinoma, may also occur as a result of reflux. Some clinical evidence supports this assumption. Individuals with a history of gastrectomy occasionally develop squamous cell carcinomas in the lower oesophagus, probably as a consequence of post-surgical reflux oesophagitis (Shearman et al., 1970;Rossi et al., 1984;Maeta et al., 1990;Seto et al., 1991). Long-lasting reflux oesophagitis following oesophageal hiatus hernia is known to be closely related to the occurrence of oesophageal cancer (Kuylenstierna & Munck-Wikland, 1985). Epidemiological studies reveal that a form of chronic oesophagitis, which is thought to result from nutritional deficiencies, is the most frequent lesion found in populations at high risk of oesophageal cancer in such areas as Kashmir in India, southern Africa, northern Iran and Linxian and Huixian in China (Cres...

The management of cervical lymph node metastases in well-differentiated carcinoma of the thyroid is controversial. In our department, from 1963 to 1972, node plucking was performed only in patients with cervical lymphadenopathy whereas, from 1973 to 1983, modified radical neck dissection was therapeutically or electively performed. In order to determine whether the more extensive dissection is adequate, a retrospective analysis was performed using two groups of patients who were managed differently with regard to the treatment of cervical lymph node metastases. From this series of 206 patients with more than five years follow-up, it was found that the rates of survival and lymph node recurrence did not differ between the two groups. However, since the well-differentiated carcinoma of the thyroid has relatively indolent biological behaviour, further long-term follow-up seems to be necessary for demonstrating the efficacy of neck dissection.

Because gastric cancers located in the upper third of the stomach are difficult to detect at an early stage, the surgical results remain poor. We performed R4 gastrectomy as a radical procedure for 25 patients, involving complete resection of the latero-aortic and interaorticovenous lymph modes above and below the left renal vein, in combination with the ordinary R2 or R3 gastrectomy (the R4 group). These patients were compared with 156 others who underwent R2 gastrectomy alone (the R2 group). There were no significant differences in operation time, blood loss, or the incidence of complications between the two groups; however, when the survival rates of the patients with tumors invading beyond the subserosa were compared, the 5-year survival rate was found to be significantly higher in the R4 group than in the R2 group. Furthermore, in patients with para-aortic nodal involvement, a significant survival advantage was observed in the R4 group, as compared with the R2 group. These results suggest that the R4 gastrectomy is a rational approach for patients with advanced gastric cancer located in the upper third of the stomach.

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