Terukazu Muto

Outcome of radical surgery for carcinoma of the gallbladder according to the TNM stage

BACKGROUND The role of surgery in the treatment of gallbladder carcinoma (GBC) is controversial. The outcome after prospective radical surgery for GBC is discussed on the basis of the TNM stage of the tumor. METHODS One hundred six patients who had undergone radical surgery were selected. The standard radical procedure consisted of a cholecystectomy accompanied by lymph node dissection, wedge resection of the liver, and resection of the extrahepatic bile ducts. The stage was determined by pathologic examination of resected specimens. RESULTS Lymph node metastases were identified in no patients with T1 tumors (n = 15), 48% of patients with T2 tumors (n = 46), 72% of patients with T3 tumors (n = 25), and 80% of patients with T4 tumors (n = 20). One patient died within 30 days after radical surgery (mortality rate, 0.9%). There were 35 5-year survivors including 11 patients with nodal involvement, 10 with stage I tumors, 13 with stage II tumors, 10 with stage III tumors, and 2 with stage IV tumors. The cumulative 5-year survival rate in patients with stage I tumors was 91% (n = 15), 85% in patients with stage II tumors (n = 24), 40% in patients with stage III tumors (n = 28), and 19% in patients with stage IV tumors (n = 39). In patients with stage III and IV tumors the 5-year survival rate was 52% after curative resection (n = 35). This was significantly better than the 5% 5-year survival rate after a noncurative resection (n = 32). CONCLUSIONS The presence of lymph node metastases is strongly influenced by the depth of invasion of the primary tumor. Accurate determination of the TNM stage is essential in comparing surgical results, predicting patient outcome, and planning additional treatment. Standard radical surgery contributes to patient survival and is recommended in patients with advanced GBC.

Relationship between gallbladder carcinoma and the segmental type of adenomyomatosis of the gallbladder

Specimens from 3197 consecutive and unselected cholecystectomies performed during a 6‐year period were studied. Adenomyomatosis of the gallbladder was defined as a lesion characterized by a thickened wall that consisted of Rokitansky‐Aschoff sinuses surrounded by proliferated fibromuscular tissue. Adenomyomatosis was found in 279 specimens and classified as one of three types: segmental, fundal, or diffuse. Segmental adenomyomatosis was found in 188 specimens; gallbladder cancer (GBC) developed in 12 (6.4%) of the patients with segmental type adenomyomatosis. GBC developed in the mucosa of the fundal compartment distal to the annular stricture of the segmental type adenomyomatosis in all 12 of these patients. Conversely, GBC developed in 93 (3.1%) of the other 3009 patients (those with fundal alone, diffuse, or no adenomyomatosis). The prevalence of GBC in patients with segmental adenomyomatosis was significantly (P < 0.025) higher than that of patients without segmental adenomyomatosis. Clinicians should be aware that segmental adenomyomatosis often coexists with GBC.

Spread of gallbladder carcinoma: CT evaluation with pathologic correlation

Abstract.Background: To assess the accuracy of computed tomographic (CT) imaging in the detection of spread and staging of gallbladder carcinoma. Methods: CT findings of spread of gallbladder carcinoma in 59 Japanese patients who underwent radical surgery were correlated retrospectively with pathologic findings. Results: The incidence of histologically proven nodal involvement was 54% (32 patients) and the most common spread of gallbladder carcinoma. The sensitivities in CT detection of N1 and N2 nodal involvement were 36% and 47%, respectively; positive predictive values were 94% and 92%, respectively. Direct extension to the liver, extrahepatic bile duct, and gastrointestinal tract or pancreas were histologically confirmed in 24, 18, and five patients. The sensitivities in the CT detection of direct spread to the liver of less than 2 cm, more than 2 cm, the extrahepatic bile duct, and the gastrointestinal tract or pancreas were 65%, 100%, 50%, and 57%, respectively; positive predictive values were 77%, 100%, 90%, and 100%, respectively. The incidence of liver metastases and involvement of interaortocaval nodes were 7% and 16%, respectively. The sensitivities in CT detection of liver metastases and involvement of interaortocaval nodes were 75% and 21%, respectively; positive predictive values were 100% and 86%, respectively. CT could not detect direct spread to omentum and peritoneal seedings. Conclusion: For detecting the spread of gallbladder carcinoma, CT imaging has low to moderate sensitivity; however, CT imaging can help in determining resectability and in planning the treatment, especially in advanced-stage gallbladder carcinoma, because of a high positive predictive value.

Intestinal fatty acid-binding protein as a sensitive marker of intestinal ischemia.

Determination of the serum level of intestinal fatty acid-binding protein has been used to detect rat intestinal ischemia following ligation or 30-min occlusion of the superior mesenteric artery. The normal values were under the minimal detectable level of less than 2 ng/ml in all the 10 rats. The serum fatty acid-binding protein level increased rapidly, to 340.7±54.6, 438.5±40.1, 388.1±37.4, and 292.2±95.7 ng/ml (P<0.01) at 1, 2, 4, and 8 hr after ligation respectively. It also increased, to 347.2±127.7 ng/ml (P<0.01) at 1 hr, after a 30-min transient occlusion and then returned to a normal level. Histological studies showed destruction of the villi, disappearance of the mucosa, and transmural necrosis with the progress of time after ligation, while no remoarkable morphological change was observed following 30-min transieent occlusion. These observations strongly suggest that the intestinal fatty acid-binding protein is a useful biochemical marker for intestinal ischemia, particularly in the early reversible phase.

Quercetin Induces Recombinational Mutations in Cultured Cells as Detected by DNA Fingerprinting

Quercetin, a fiavonoid, is found in many fruits and vegetables. This drug was previously shown to affect the metastatic potential of mouse tumor cells. Mutagenicity of quercetin was examined by means of DNA fingerprint analysis using the Pc‐1 probe that efficiently detects mutations due to recombination. Treatment of BMT‐11 and FM3A tumor cells with 55 μM quercetin resulted in gain and loss of bands in the fingerprints in both cell lines. The frequencies of the clones having undergone mutation were 3/11 and 6/26, respectively. This suggests that quercetin is mutagenic and induces recombination. This result seems to provide a molecular basis for the phenotypic variations of BMT‐11 tumor cells induced by quercetin.

Electrogastrography prior to and following total gastrectomy, subtotal gastrectomy and gastric tube formation

On electrogastrography (EGG) spectral analysis, an activity of 3 cycles per minute (cpm) is supposed to be specific for the stomach. After total or subtotal gastrectomy, the original site of the stomach is occupied mainly by the intestine. We attempted to determine if intestinal activity could be recorded in this region with EGG. Epigastric recordings were performed in patients prior and following gastrointestinal or control surgeries. Spectral analysis, using the maximal entropy method and ensemble means was applied to data analysis from these recordings. Preoperatively, the majority of the power peaks were found around 3, 6, and 11 cpm. The postprandial-to-fasting power ratio of all of these power peaks increased significantly postprandially (P<0.05–0.01). Following total gastrectomy, the power peak around 3 cpm disappeared or was significantly diminished in amplitude (P<0.05). The postoperative-to-preoperative power ratio ranged from 0.03 to 0.10 (P<0.001–0.01). However, the power peak around 11 cpm did not significantly change prior to or following total gastrectomy, and the 11 cpm peak appeared relatively dominant. Simultaneous manometric studies in the Roux limb demonstrated a correlation between the power spectral frequency of EGG and manometry at 11 cpm. Therefore, the 11 cpm peak appeared to reflect jejunal or Roux limb electrical activity. The postoperative to preoperative power ratio for the 3 cpm also was significantly reduced following subtotal gastrectomy and gastric tube formation in patients in the postprandial state (P<0.05–0.001).

Superficial spreading carcinoma of the esophagus

Superficial spreading type of carcinoma of the esophagus was defined as lesions with an intramucosal extension of carcinoma 20 mm or more from the main lesion. Eleven (6.1%) of 179 cases were thus selected for this investigation. These cases were further divided into two groups: Group A, consisting of four cases (2.2%) with the main lesion confined to the submucosa, representing a relatively early stage; and Group B, consisting of seven cases (3.9%) with the main lesion invading the muscular layer or deeper. One of the most characteristic features in the four cases belonging to Group A was an unexpectedly high incidence of lymphatic permeation and lymph node metastases leading to a poor prognosis. Another feature that may be important, particularly for surgeons performing esophagectomy, was the difficulty in deciding the proximal resection line of the esophagus because the boundaries between involved and uninvolved portions were frequently indistinguishable in this particular pathologic entity, not only in Group A but in Group B.

The mode of lymphatic spread in carcinoma of the bile duct

BACKGROUND Knowing the prevalence of lymph node involvement associated with the location of the primary tumor is a prerequisite for operating with curative intent in carcinoma of the bile duct. METHODS We evaluated 80 patients with carcinoma of the bile duct or cystic duct to investigate the frequency of lymph node involvement, the mode of lymphatic spread, and prognosis, according to the location of the primary tumor. RESULTS The frequency of lymphatic spread of carcinomas in the proximal, middle, and distal bile ducts, excluding seven T1 tumors, was 48%, 67%, and 56%, respectively. With regard to the mode of lymphatic spread: (1) a metastatic pathway along the common hepatic artery predominated over that to the retropancreatic area in the proximal duct carcinoma group; (2) in the middle duct carcinoma group, metastatic lymph nodes were distributed widely, involving nodes around the superior mesenteric artery or at the para-aortic area; and (3) in the distal duct carcinoma group, metastatic nodes generally were localized around the head of the pancreas. CONCLUSIONS Understanding the mode of the lymphatic spread according to the primary tumor may be helpful for choosing the appropriate surgical approach with curative intent in bile duct carcinoma.

Possible role of rat fatty acid-binding proteins in the intestine as carriers of phenol and phthalate derivatives

Fatty acid-binding proteins of hepatic and intestinal type and gastrotropin-like protein (GTLP) were purified from rat intestinal cytosol by Sephadex G-75 gel filtration and DEAE-cellulose, CM-cellulose, and hydroxylapatite chromatographies. In addition to fatty acids, butylated hydroxytoluene (BHT), phthalate dibutyl, and di(2-ethylhexyl) esters (DBP and DEHP) were identified by gas liquid chromatography and mass spectrometry as endogenous ligands from the extract of either fatty acid-binding protein superfamily. These protein families in the intestine may have an important role as carriers in the initial step of arresting these exogenous pollutants.

HEPATIC BRANCH VAGOTOMY CAN SUPPRESS LIVER REGENERATION IN PARTIALLY HEPATECTOMIZED RATS

The role of the vagus nerve in liver regeneration after partial hepatectomy was studied by comparing the effects of hepatic branch vagotomy with those of hepatic branch sympathectomy in rats. The liver weight as a percentage of body weight decreased significantly 7 days after vagotomy compared with the controls and this was associated with a reduction in food intake. There was no difference in the liver weights between the control rats and the pair-fed vagotomized rats. Hepatic sympathectomy had no significant effect on the liver weight. The serum scores indicating hepatic function showed no difference between the control and the vagotomized rats except alkaline phosphatase. The concentration of insulin was unchanged. The number of mitotic hepatocytes remained high at 7 days after vagotomy. These observations led us to conclude that the vagus nerve stimulates liver regeneration, and its effect depends on vagal factors directly and specifically.