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...
We performed continuous hyperthermic peritoneal perfusion (CHPP) or continuous normothermic peritoneal perfusion (CNPP) combined with cisplatin (CDDP) 300 mg/kg and mitomycin C (MMC) 30 mg/kg in an attempt to prevent peritoneal recurrence after surgery for gastric cancer. Twenty-two patients were treated with perfusion using about 10 liters of saline heated to 41 degrees to 42 degrees C (CNPP group); 18 patients were treated with saline heated to 37 degrees to 38 degrees C (CNPP group); and 18 patients underwent only gastric surgery without perfusion (control group) in a randomized control study. There were two deaths (9%) due to peritoneal recurrence in the CHPP group, four (22%) in the CNPP group, and four (22%) in the control group. The 1-, 2-, and 3-year survival rates were 95%, 89%, and 68%, in the CHPP group; 81%, 75%, and 51%, in the CNPP group; and 43%, 23%, and 23%, in the control group, respectively. There was a significant difference between the three survival curves by the log-rank test (p < 0.01). This difference showed that CNPP and CHPP are both effective procedures for preventing peritoneal recurrence. The maximum concentrations in the perfusate of total and free CDDP with 300 mg administration were 12.2 and 10.1 micrograms/ml, respectively, at the end of the perfusion, and the maximum concentrations of total and free CDDP in plasma were 2.1 and 1.0 micrograms/ml, respectively. The maximum concentrations of MMC in perfusate and plasma with 30 mg administration were 1.00 and 0.05 micrograms/ml, respectively, which are intraperitoneally cytotoxic but systemically safe concentrations.
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...
Summary The incidence of nodal metastasis in early gastric carcinoma (EGC) is 10-20%. However, the optimal nodal dissection for early gastric carcinoma has not been established. A retrospective study was conducted in 392 consecutive patients who underwent potentially curative distal gastrectomy for EGC between 1962 and 1990. Of these 295 patients treated after September 1972 were prospectively entered into an extensive lymphadenectomy protocol. These patients were compared with 97 patients with simple gastrectomy in respect of the causes of death after surgery and the 10 year disease-specific survival rate. The incidence of nodal metastasis in early gastric carcinoma patients was 13.0%. Operative mortality from extensive lymphadenectomy was almost the same as from simple gastrectomy (2.0% and 2.1% respectively). Extensive al., 1987; Ohta et al., 1987; Marczel et al., 1988;Lehnert et al., 1989;Percivale et al., 1989;Farley et al., 1992;Maehara et al., 1993). Nevertheless, the optimal extent of lymph node dissection for EGC has not been well established. Japanese surgeons normally perform extensive lymphadenectomy for EGC because a certain proportion of these patients have lymph nodal involvement and carcinoma recurrence is not rare. In contrast, most surgeons in Western countries do not use aggressive surgery (Cuschieri, 1986;Heberer et al., 1988;Irvin and Bridger, 1988;Heesakkers et al., 1994), perhaps because of uncertainty regarding improvement in the survival rate and the high operative risk associated with extensive lymph node dissection (Dent et al., 1988;Heberer et al., 1988;Irvin and Bridger, 1988).To evaluate the therapeutic value of extensive lymphadenectomy in EGC, we analysed retrospectively the causes of death after surgery and compared the 10 year disease-specific survival rate in patients who had received extensive lymphadenectomy with patients who had received simple gastric resection. (LLND). ELND was performed beginning in September 1972. The LLND group consisted of 68 patients before September 1972 and 29 patients after. Each surgical procedure is outlined below. The subjects were followed up, and the effect of lymph node dissection on their 10 year disease-specific survival was evaluated. The operative and pathological findings were assessed according to the guidelines of the Japanese Research Society for Gastric Cancer (1981). The median age of the patients at the time of operation was 59 years, with a range of 18-84 years. There were 271 males (69%) and 121 females (31%). SurgeryThe ELND gastrectomy was performed as follows: the entire greater omentum, superior leaf of the mesocolon, pancreatic capsule and lesser omentum were removed en bloc with the cancerous distal portion of the stomach. Each of the supplying gastric arteries was ligated and divided at its origin, and the group 1 lymph nodes (nl), namely those along the lesser and greater curvatures, as well as the supra-and infra-pyloric lymph nodes, were completely dissected. In addition, the group 2 lymph nodes (n2) located at the...
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