Pancreatic ductal myofibroblasts. Proliferative patterns in various pathologic situations.

Myofibroblasts in the periacinar area of the pancreas have been demonstrated to mediate fibrogenesis in pancreatic fibrosis. However, only a few reports have described myofibroblasts in the pancreatic duct. To elucidate the presence of myofibroblasts in the pancreatic ductal wall, we performed an immunohistochemical study, using immunostains for both alpha-smooth muscle actin (alphaSMA) and desmin, and an electron microscopic study on surgically resected pancreatic specimens from 10, 23, 23, and 56 cases of focal pancreatitis (FP), chronic pancreatitis (CP), pancreatic carcinoma (PCa), and carcinoma of the papilla of Vater (VPCa), respectively. All cases showed localized stenosis of the main pancreatic duct by means of preoperative pancreatography. As controls, 20 autopsy cases were studied. alphaSMA-positive and desmin-negative cells existed in the ductal walls of controls and were revealed as myofibroblasts by means of electron microscopy. In six FPs, proliferation of myofibroblasts was observed at the stenotic portion. In VPCas, myofibroblasts mainly proliferated in the pancreatic ductal wall. In CPs and PCas, no myofibroblast proliferation was observed at the stenotic portion. The proliferation of myofibroblasts might occur as a wound healing process in FP, while acting against elevation of intraductal pressure in VPCa. In conclusion, proliferation of myofibroblasts plays an important role in ductal changes in various pathological situations.

Adenocarcinoma of the gastroesophageal junction in Japan: relevance of Siewert's classification applied to 177 cases resected at a single institution.

BACKGROUND: There had been a lack of international consensus about the definition of cancer of the gastric cardia until Siewert's classification was approved at a consensus conference during the second International Gastric Cancer Congress held in 1997. STUDY DESIGN: A review of the prospective gastric cancer database at Aichi Cancer Center from 1983 to 1992 identified 1,913 gastric carcinoma patients who underwent gastrectomy. These patients were classified retrospectively according to the Siewert classification, and 177 patients who fell into one of the three types form the basis of this study. Survival analyses were performed after stratifying patients by clinicopathologic variables. RESULTS: There were 33 patients with type II and 144 with type III, although none had type I, a type frequently observed in the west. No evidence of a change in the frequency of types II or III cancers (approximately 9.3% overall) among gastric carcinoma patients was observed over the 10-year period. Clinical staging of gastric carcinoma by the TNM classification was found to reflect accurately the prognosis of these patients. There were no longterm survivors among the few patients with metastasis to the perigastric nodes of the distal stomach. CONCLUSIONS: A striking difference in the distribution of types of adenocarcinoma of the gastroesophageal junction was observed in Japan compared with previously reported western data. A subgroup of carcinoma of the proximal stomach identified as types II and III may not require proximal gastrectomy from the viewpoint of sufficient lymphadenectomy.

Metastatic gastric lymph node rate is a significant prognostic factor for resectable stage IV stomach cancer.

BACKGROUND: Stage IV gastric carcinoma is rarely curatively resected and almost invariably carries a poor prognosis. Several clinicopathologic factors are involved, but lymphatic spread of the cancer may significantly affect survival. STUDY DESIGN: A retrospective study was designed to evaluate whether the nodal metastatic rate (number of lymph node metastases/number of resected lymph nodes) is a parameter of lymphatic spread and could provide a significant prognostic factor. Several prognostic factors were assessed by multivariate analysis in 153 stage IV gastric carcinoma patients with histopathologic data on nodal metastasis. RESULTS: A significant difference in survival was observed in the stage IV cancer patients with total nodal or gastric nodal metastatic rates < 50% versus those with rates > 50%. Multivariate analysis revealed that a total nodal or gastric nodal metastatic rate > 50% was a highly significant prognostic factor. The gastric nodal metastatic rate can be used in patients who do not undergo an extended lymphadenectomy. CONCLUSIONS: Lymphatic spread of gastric carcinoma expressed in terms of the total nodal or gastric nodal metastatic rate is a significant prognostic factor. The latter can be calculated without pathologic data derived from extended lymphadenectomy, and so it is universally applicable.

Surgical treatment of Borrmann type IV gastric carcinoma: relevance of lymphadenectomy in improving survival.

BACKGROUND: Borrmann type IV gastric carcinoma carries a poor prognosis, even if curatively resected. The benefit of a lymphadenectomy is unknown. STUDY DESIGN: A retrospective study was designed to evaluate whether improvements have been made in the treatment of type IV gastric carcinoma over the past decade. The 345 patients with type IV carcinoma who underwent laparotomy within a recent 16-year period were split into two groups: one group of patients who underwent laparotomy between 1977 and 1985, and the other between 1986 and 1992. Survival data were compared between these two groups and prognostic factors for type IV gastric carcinoma were assessed by multivariate analysis. RESULTS: A significant difference in survival was observed between the groups, both of which underwent curative resection, despite a lack of difference in background factors. The improvement was more prominent among patients with nodal metastases and insignificant among patients without nodal metastases. Multivariate analysis identified nodal metastasis as a major independent prognostic factor. CONCLUSIONS: An improvement in outcome was presumably achieved through extended lymphadenectomy. However, the survival rate remains unsatisfactory, and further advances in the treatment of this disease are needed.

The number of metastatic lymph nodes: a promising prognostic determinant for gastric carcinoma in the latest edition of the TNM classification.

BACKGROUND: The number of metastatic regional lymph nodes determines the new pN categories in the 5th edition of the TNM classification. STUDY DESIGN: Our retrospective study was conducted to compare the new method of defining lymph node status with the conventional classification, consisting of the anatomic extent of lymph node metastases, a well-established prognostic factor. The study was based on clinical data for 493 patients with gastric carcinomas who underwent potentially curative operations and had histologically confirmed nodal metastases. These patients were stratified into 1) n categories according to the Japanese Classification of Gastric Carcinoma, 2) the new pN categories, and 3) the pN categories determined by the number of metastatic perigastric nodes resected by standard D1 gastrectomy. Survival data were analyzed for each group. RESULTS: The number of metastatic nodes after D2 lymphadenectomy reflected prognosis well and was shown by multivariate analysis to be a strong independent prognostic factor. When the classification was performed limited to the metastatic perigastric nodes, stage migration was evident, but the variable remained competent as a prognostic indicator. CONCLUSIONS: The number of metastatic nodes is a promising determinant in the new international stage classification.

Visualization of routes of lymphatic drainage of the gallbladder with a carbon particle suspension.

BACKGROUND: Although carcinoma of the gallbladder frequently spreads lymphatically, few reports exist about the evaluation of routes of lymphatic drainage of the gallbladder by vital staining. The purpose of this study was to visualize drainage routes and the extent of lymphatic flow from the gallbladder by using vital staining with a carbon particle suspension (CH40). STUDY DESIGN: In 20 patients, 0.3 to 0.5 mL of carbon particle suspension was injected into first station nodes for the gallbladder, the cystic node or pericholedochal node, intraoperatively. After a Kocher maneuver was performed, lymph nodes and lymphatic vessels blackened by the stain were visualized macroscopically. RESULTS: Lymphatic pathways from the gallbladder were classified into three routes: right, left, and hilar. The right route, which ran along the common bile duct to the superior retropancreaticoduodenal node or the retroportal node and reached the para-aortic nodes, was stained in 95 percent of patients. The left route, which traveled toward lymph nodes medial to the hepatoduodenal ligament through the posterior aspect of the head of the pancreas, was stained in less than 50 percent of patients. Among lymph nodes along the left route, the posterior common hepatic node was most frequently stained (45 percent). The hilar route, which ascended toward the hepatic hilus, was stained in 20 percent of patients. CONCLUSIONS: These data demonstrate that the right route is a main pathway of lymphatic drainage from the gallbladder, while the left and hilar routes are branch lines. The para-aortic nodes, regarded as final regional nodes for the gallbladder, should be removed during radical surgery for advanced carcinoma of the gallbladder. Drainage along the hilar route may cause metastasis to the liver.

Gastric remnant carcinoma after partial gastrectomy for benign and malignant gastric lesions.

BACKGROUND: A retrospective study was designed to evaluate the clinicopathologic characteristics and prognosis of gastric stump carcinoma (GSC) after gastrectomy for gastric adenocarcinoma. STUDY DESIGN: A comparison of the clinicopathologic features was made between 12 cases of GSC and 27 cases of remnant carcinoma (RC) following gastrectomy for adenocarcinoma. The various factors influencing survival of both groups of patients were evaluated separately and by multivariate analysis. RESULTS: Gastric stump carcinoma emerges late after initial gastrectomy and has a significant tendency toward lymph node metastasis. No difference was observed between the survival curves for patients with GSC or RC after gastrectomy for malignancy. Serosal invasion was the factor most affecting survival. CONCLUSIONS: Early diagnosis is most important for management of the disease, and only patients with T2 staged GSC according to the Union Internationale Contre le Cancer classification system might benefit from extensive lymphadenectomies.

Clinical trial of prophylactic endoscopic variceal ligation for esophageal varices.

Endoscopic variceal ligation is an effective therapy for variceal bleeding, and use of the method has recently been increasing. We evaluated the clinical usefulness of prophylactic endoscopic variceal ligation. Twenty-two patients with enlarged, tortuous varices and "red color signs" were selected. These patients were treated with ligation therapy alone and the varices were eradicated, i.e., reduced to small, straight varices without red color signs. Ligation therapy was withdrawn if the general condition of the patient worsened or if the varices could not be removed by suction. Follow-up endoscopy was performed every 4 months, and another ligation was performed if there were recurrent varices or variceal bleeding. The total reduction rate was 86.4%, and eradication required two sessions of therapy and 30 days of hospitalization on average. Complications included esophageal injury in 1 patient and treatment-induced bleeding in 1 patient; both complications were easily controlled. No variceal bleeding occurred after the eradication. There was no mortality due to gastrointestinal bleeding during the median follow-up period of 346 days. Prophylactic endoscopic variceal ligation made it possible to prevent fatal variceal bleeding with a minimum risk of complications, suggesting that this could be an alternative method for the prevention of first-time variceal bleeding.

Tumor localization as a prognostic factor in hepatocellular carcinoma.

We investigated the significance of tumor localization as a contributory factor in the prognosis of hepatocellular carcinoma. A trend toward a better survival rate was noted in the 57 patients whose tumors were confined to the left hepatic lobe [left lobe group] as compared with the 146 patients whose tumors were located strictly in the right hepatic lobe [right lobe group]. The difference in survival was significant (p < 0.02) in stage I and stage II disease, but equivalent survival rates were seen in stage III and stage IV disease. The right lobe group patients with stage I or stage II disease who underwent lobectomy or segmentectomy had a better survival rate than those undergoing subsegmentectomy or limited resection (p < 0.001). But in the left lobe group, no difference was observed with various operative procedures. These results lead us to speculate that tumor localization might be a contributory factor in the postoperative prognosis, and an important determinant of the operative approach to hepatocellular carcinoma.

[Comparison of therapeutic effects of SMANCS (+TAE) and Non-SMANCS/LpTAE].

Therapeutic effects of SMANCS and LpTAE were evaluated for hepatocellular carcinoma (HCC). Since June 1995, SMANCS has been used in 59 patients for their first treatment. LpTAE had been performed for HCC before introduction of SMANCS in our hospital, and 71 patients treated after 1992 were chosen for comparison with the therapeutic effect of SMANCS. Among the patients treated with SMANCS, complete and partial responses (CR and PR) were obtained in 24 cases (41%) and 17 cases (33%), respectively. SMANCS accompanied by TAE was more effective than SMANCS alone. The effects did not depend on the level of the hepatic arterial branch at which SMANCS was administered. In patients treated with LpTAE, CR and PR were obtained in 12 cases (17%) and 18 cases (25%), respectively. SMANCS was significantly more effective than LpTAE. Because of our short experience with SMANCS, we could only show a two year survival rate. The one- and two-year survival rates for SMANCS were 71% and 57%, respectively. They were not significantly different from those for LpTAE, at 80% and 60%. Despite good results of treatment for HCC, a better prognosis could not be expected by SMANCS in this study. These results may be explained as follows. The evaluating the cause of death within two years after first treatment, hepatic failure was more common in patients treated with SMANCS. After treatment by SMANCS, 11 patients (55%) died from hepatic failure. On the other hand, 4 patients (15%) died from hepatic failure after LpTAE. Although there is no significant difference of Child Pugh score, this may indicate that SMANCS has been used for patients with lesser hepatic reserve and this leads to early deaths in patients treated with SMANCS. However, because of the short experience in this study, further observation is necessary for precise evaluation of clinical efficacy of SMANCS.

[Alternations of p53 gene, microsatellite instability and proliferation associated antigen Ki-67 in the synchronous multiple colorectal cancers].

To evaluate the malignant potential of synchronous multiple colorectal cancers, we studied clinicopathologically 31 synchronous multiple colorectal cancers resected at our hospital. We also compared the p53 gene mutation rate, replication error (RER) rate, and Ki-67 antigen positivity rate between these cancers and 90 sporadic colorectal cancers. There was no significant difference in lymphoid and venous invasion, hepatic metastasis, or stage of colon cancer between the two types of cancers. The p53 gene mutation rate was lower in synchronous multiple colorectal cancers (p < 0.05). The RER rate and positivity rate for Ki-67 antigen was significantly higher in these cancers (p < 0.05). These results suggest that some synchronous multiple colorectal cancers result from carcinogenesis in which RER genes are involved, as HNPCC does. In the patients with synchronous multiple colorectal cancers, it is clinically important to follow them carefully focusing on multiple metachronous colorectal cancers and multiple organ cancers.

[Clinical evaluation of endoscopic variceal ligation (EVL)].

From August 1992 through February 1993, we treated 21 patients with endoscopic variceal ligation (EVL). Two patients had a history of the esophageal variceal bleeding, but 19 patients did not have bleeding episodes. To evaluate preventive effect of bleeding, we selected the patients who had grade F2 or red color sign positive varices. We repeated EVL until varices improved into grade F0 or F1 and red color sign negative. The therapeutic goal was sometimes changed according to patient's general condition. No additional therapy was performed to eradicate varices, such as endoscopic injection sclerotherapy. As a result of our therapy, eradication rate was 73.7% and period of hospitalization were 25 +/- 11 days. No major complications were found during and after EVL. EVL affected neither liver function test nor size of gastric varices. Recurrent varices with red color sign were found in 4 patients, but easily controlled by retreatment with EVL. EVL seems to be convenient and effective therapy in our short-term study, and useful for preventive therapy of the esophageal variceal bleeding.

[A basic study on gastric emptying test using barium grains and effect of drugs on gastric emptying in rats].

We reported an experimental study on a new non-invasive method for evaluation of gastric emptying by abdominal X-ray after administration of radiopaque barium grains. Adult male Wistar rats weighing around 200 g were used. After they were fasted for 24 hours, 1 ml of gruel mixed with 10 barium grains (1 mm diameter) was introduced into the rat stomach with a catheter. The rats were sacrificed at 30, 60, 90, 120 and 150 minutes after the introduction of the gruel. X-rays were taken at each time point and grains in the stomach were counted in the X-ray photographs. All barium grains were emptied from the stomach in 150 minutes. After incision of the abdomen, the residual gastric contents were weighed. A positive correlation was found between the grains in the stomach and the weight of the contents. We studied the effects of cisapride, scopolamine buthylbromide and enprostil on the gastric emptying time by this method. Cisapride accelerated gastric emptying, whereas scopolamine buthylbromide delayed it. A prostaglandin E2 analog, enprostil delayed the gastric emptying. This method was found to be a simple procedure which is outstanding for quantitative determination and useful in evaluating gastric emptying functions.