Doubling time of serum CA 19-9 in the clinical course of patients with pancreatic cancer and its significant association with prognosis.

BACKGROUND AND OBJECTIVES: Pancreatic cancer is generally a disease with a poor prognosis, and relationship between change of serum CA 19-9 level and progression of this disease was investigated with regard to clinical pace of disease and tumor growth. METHODS: CA 19-9 doubling time was examined in 75 patients with pancreatic cancer, including 41 inoperable cases. Then, its relation with their prognosis and change in tumor was evaluated. RESULTS: The doubling time of CA 19-9 and CEA could be calculated in 90.2% and 58.5% of patients with inoperable pancreatic cancer. CA 19-9 doubling time was clearly associated with survival time in inoperable and palliatively operated cases, but not with sex, age, site of the lesion, or liver metastasis, and was significantly correlated with the tumor volume doubling time. CONCLUSIONS: Examination of CA 19-9 doubling time may be useful in clinical evaluation of the prognosis for patients with pancreatic cancer and could possibly prove valuable in terms of the analysis of the growth process in this disease.

[Complete remission of liver metastasis from rectal cancer following continuous oral administration of tegafur-uracil after intrahepatic arterial single injection of CDDP and 5-FU].

An intrahepatic arterial injection of CDDP, 5-FU, followed by ten months of oral tegafur-uracil administration (2g/day), induced remission for 3 months or more in a 72-year-old male with rectal cancer and synchronous liver metastasis subsequent to anterior resection of the rectum. Tegafur-uracil showed an excellent anticancer effect against colorectal metastatic liver cancers without loss of QOL because a single-low dose of intraarterial anticancer injection was followed by continuous oral administration of tegafur-uracil, and the chemotherapy could be managed to obtain complete remission of the hepatic lesion.

Flow cytometric analysis of nuclear DNA content in the endoscopic biopsy tissues of gastric cancer.

The nuclear DNA content was measured by flow cytometry in gastric cancer patients using endoscopically biopsied tissue specimens. When the specimens were classified into diploid and aneuploid according to the DNA histogram, 56% (65/117) of the specimens were aneuploid, and advanced cancer was clearly more often aneuploid than early cancer. The frequency of aneuploidy appeared to be higher as the histologic depth of cancer was greater. Noncancerous tissues of the stomach were mostly diploid. The nuclear DNA ploidy pattern in gastric cancer cells could be analyzed by using endoscopic biopsy samples and this flow cytometric investigation would be possibly contributive to further characterization of gastric cancer in the diagnostic procedure of malignancy.

Flow cytometric analysis of nuclear DNA content in tissues of colon cancer using endoscopic biopsy specimens.

Flow cytometric assay of nuclear DNA in endoscopic biopsy specimens was evaluated in colon cancer patients. When the cells were divided into diploid cells and aneuploid cells, aneuploidy was observed in 63% (58 of 92) of the colon cancer patients. However, no clear relation was observed between the frequency of aneuploidy and the invasive depth, size, or histological type of colon cancer. Noncancerous portions of the colon tissues including colon adenoma or normal mucosa were mostly (96%, 87 of 91) diploid. Nuclear DNA content could be analyzed in the fresh biopsy specimens of colon cancer tissues and such investigation might be possibly valuable for further biological characterization of colon cancer in the usual procedure of clinical diagnosis for colonic malignancy before surgical operation or other treatment.

Two cases of pancreatic cystadenocarcinoma with elevated CA 19-9 levels in the cystic fluid in comparison with two cases of pancreatic cystadenoma.

A 39-year-old woman was hospitalized with left hypochondralgia. Ultrasonography and abdominal computed tomography showed a cystic mass in the tail of the pancreas. Echo-guided aspiration of the cyst was performed, and a markedly elevated CA 19-9 level in the cystic fluid was found. A surgical operation was performed, and the tumor was radically resected. The pathologic diagnosis was papillary adenocarcinoma of the pancreas. Another case of pancreatic cystadenocarcinoma also had an extremely high cystic CA 19-9 level, whereas two cases with benign pancreatic cysts had very low cystic CA 19-9 levels. Moreover, positive localization of CA 19-9 in the cancerous tissue was clearly demonstrated by an immunohistochemical technique, indicating active secretion of CA 19-9 into the cyst, while CA 19-9 in the tissue of pancreatic cystadenoma was almost non-existent. Measurement of the CA 19-9 level in the cystic fluid might therefore be a valuable additional aid in the diagnosis of cystadenocarcinoma of the pancreas.

[A case of recurrent sigmoid colon cancer successfully treated with 5-FU and UFT].

A 57-year-old female patient with recurrent sigmoid colon cancer was successfully treated with 5-FU and UFT for 8 years. The patient, with cancer recurrence in the para-aortic lymph nodes, which were palpated in the abdomen, was given oral 5-FU at a daily dose of 200 mg. During the second week of administration, the mass showed a remarkable decrease in size, and complete disappearance was achieved within one month. However, 5 years and 2 months after discontinuation of 5-FU administration, recurrence in the supra-clavicular lymph nodes and para-aortic lymph nodes was recognized. After administration of UFT at a daily dose of 600 mg, complete disappearance of para-aortic lymph node recurrence was observed. At present, the patient is under observation as an outpatient at our hospital. This case suggests the effectiveness of 5-FU and UFT for lymph node metastases of sigmoid colon cancer.

Detection of gastric cancer by a combination of tissue polypeptide antigen (TPA), lipid-bound sialic acid (LBSA) and carcinoembryonic antigen (CEA).

In this study, the clinical significance of the tumor markers, tissue polypeptide antigen (TPA) and lipid-bound sialic acid (LBSA) in conjunction with carcinoembryonic antigen CEA, was tested in 52 gastric cancer patients. The incidence of elevated serum levels of these 3 markers was as follows: 63% (33/52) for TPA; 40% (21/52) for LBSA; 21% (11/52) for CEA. In a combination assay using all three tumor markers, 37 out of 52 gastric cancer patients (71%) showed a positive combination assay, while 5 out of 20 normal subjects (25%) showed a positive combination assay. In a discriminant analysis of the resulting data, 18 out of 52 gastric cancer patients (35%) were classified correctly based on an analysis of CEA alone. Furthermore, 25 out of 52 gastric cancer patients (48%) and all 20 normal subjects (100%) were classified correctly based on an analysis of all three variables. Our data suggest that TPA and LBSA are more sensitive than CEA as markers of gastric cancer, and that the simultaneous measurement of TPA and LBSA in conjunction with CEA is more useful in cancer detection than the measurement of CEA alone.

Manometric study and prolonged pH monitoring of esophagus in patients with hiatus hernia before and after operation.

The pathophysiology of the lower esophagus in 18 patients with hiatus hernia and 15 normal controls was investigated by esophageal manometry and prolonged pH monitoring. Thirteen patients with symptoms of severe gastroesophageal reflux had lower than normal pressures at the gastroesophageal junction. In 5 patients without symptoms, the pressure was normal. Nine of the 13 patients were inadequately controlled by conservative measures and underwent Nissen or Dor-Nissen fundoplication. All were free of esophageal symptoms postoperatively. Fundoplication resulted in a significant increase in the lower esophageal pressure. Prolonged esophageal pH monitoring showed significant improvement in all indices. Hiatus hernia and gastroesophageal reflux are related etiologically. However, further observations are needed to explain the association between reflux esophagitis and hiatus hernia. Nissen and Dor-Nissen fundoplications restored competence to the gastroesophageal junction as judged by esophageal manometry and prolonged pH monitoring.

Prevention of gastroesophageal reflux using Nissen fundoplication in the staged repair of esophageal atresia with distal tracheoesophageal fistula.

To prevent the reflux of gastric contents into the bronchial tree through the tracheoesophageal fistula in patients with esophageal atresia with tracheoesophageal fistula, Nissen fundoplication was performed in the first-stage repair of staged operations. After elimination of the pulmonary complication, a correction of esophageal atresia and tracheoesophageal fistula was successfully performed through the extrapleural route at the age of 16 days. Thus, because Nissen fundoplication is simple to perform and effective in preventing gastroesophageal reflux, this procedure is considered to be useful in the staged repair of esophageal atresia with tracheoesophageal fistula.

Studies on effect of carcinoembryonic antigen on leucocyte migration inhibition test in patients with colorectal cancer.

Leucocyte migration inhibition test (LMIT) is a useful method to detect tumor associated antigens (TAA) in cancer patients. Carcinoembryonic antigen (CEA) is one of the best tumor markers for gastrointestinal cancer, and especially for colorectal cancer patients, who show high plasma CEA level frequently. In this study, we performed LMIT in 71 colorectal cancer patients with 3 M KCl extracts of cancer tissues and measured concentration of CEA in the plasma and the extracts of cancer tissue simultaneously. Although CEA in colorectal cancer extracts was individually varied from low to high in concentration, the levels of CEA had no relation to LMI reactivity. In addition, the LMI reactivity of colorectal cancer patients did not relate to the plasma CEA level of the corresponding patient. The results suggest that some antigens which induce leucocyte migration inhibition factor (LMIF) to lymphocytes from colorectal cancer patients might be different substances from CEA.

Anal sphincter function and rectal reservoir after sphincter saving operations for carcinoma of the rectum.

Anal sphincter function and rectal reservoir were studied in 27 patients after low anterior resection, in 6 after Welch or Turnbull type pull-through surgery and in 3 after Bacon type pull-through surgery. Sixteen patients who had undergone right hemicolectomy served as a control group. Anal sphincter function immediately after low anterior resection was diminished, but improved during the following 6 months. Rectal capacity was much reduced immediately after surgery, but increased with time, and the neorectum could to some extent adapt to its new role as a reservoir. After pull-through operations, anal canal pressure and rectal compliance were significantly lower than after low anterior resection or right hemicolectomy. These findings may explain the increased frequency of bowel action after pull-through operations.

Immunoassessment of patients with gastric cancer. Using leukocyte migration inhibition (LMI) test.

Leukocytes from patients with gastric, colorectal or benign gastrointestinal disease, as well as those from normal control subjects, were tested by the leukocyte migration inhibition test (LMIT), using five different allogeneic 3 M KCl extracts of gastric cancer extracts. In LMIT with a single tumor extract, a pathological MI was found in 48% of 79 gastric cancer patients, a significantly higher figure than in the three other groups of patients (4-21%). In the panel mode of LMIT, that is, testing each blood sample with five different tumor extracts, 62/79 (79%) of patients with gastric cancer showed a positive reaction. Positive reactivity was significantly higher in patients with gastric cancer than in patients in the other groups and the frequency was higher in stage IV cases than in stage I-III cases, although the differences were not significant. In addition, the frequency of the positive reaction was unrelated to the degree of differentiation in adenocarcinoma. Positive reactivity increased in inverse proportion to the degree of nuclear grade (NG) (84% in NG I, 80% in NG II and 64% in NG III), but the correlation was not statistically significant.

Immunoreactive carcinoembryonic antigen in gastric juice in patients with gastric cancer.

To clarify the significance of immunoreactive carcinoembryonic antigen in gastric juice (gastric CEA) from gastric cancer patients, we studied the gastric CEA in comparison with cancer progress, histologic types of tumors, staining for CEA and extent of intestinal metaplasia. The gastric CEA levels from patients with other gastric diseases, i.e., gastric ulcer, duodenal ulcer and chronic gastritis were also investigated. The mean gastric CEA level from gastric cancer patients was significantly higher than from gastric or duodenal ulcer patients, but there was no significant difference between levels in patients with gastric cancer and in those with chronic gastritis. The gastric CEA levels from cancer patients increased with progression of the cancer. The differentiated carcinomas showed significantly higher gastric CEA levels than the poorly differentiated carcinomas. Positive CEA tumors showed significantly higher gastric CEA levels than did the negative CEA tumors. The tumors with diffuse intestinal metaplasia revealed high gastric CEA levels. Determination of gastric CEA levels is considered to be useful for screening of gastric cancer.

Conservative surgery for regional lymphadenectomy in the treatment of early gastric carcinoma.

The relationship between lymph node metastases and postoperative prognosis in 209 patients with early gastric cancer was studied. As to the postoperative prognosis in relation to the extent of lymph nodes dissection, no significant difference was observed among the age-corrected 5-year survival rates following three surgical procedures in patients with early gastric cancer. Age-corrected 5-year survival rates were 0.92 +/- 0.44 R1-resection, 0.95 +/- 0.44 in R2-resection, and 1.00 +/- 0.06 in R3-resection, respectively. In addition, in 71 patients including 33 with early gastric cancer and 38 patients with advanced but relative early gastric carcinoma, the relationship between the immunostatus and postoperative prognosis was investigated. Postoperative age-corrected 5-year survival rate (0.904 +/- 1.153) of the optimal responders with good immunostatus was significantly higher than that (0.582 +/- 1.153) of the suboptimal responders with impaired immunostatus (P less than 0.01). Thus, conservative surgery for regional lymphadenectomy may be an effective procedure for cure of early gastric carcinoma, particularly in cases of a carcinoma limited to the mucosal area of the stomach.

Antigenicity of a fetal extract in the leucocyte migration-inhibition test.

Leucocytes from patients with gastric or colorectal cancer as well as from normal subjects were tested by the leucocyte migration-inhibition test against 3 M KCl extracts of three whole fetuses and eight fetal gastrointestinal tract tissues. The incidence of pathologic results in patients with gastric and colorectal cancer was 26% (25/77) and 34% (25/74), respectively. The values were significantly higher than those of normal subjects (3%, 1/30). No significant difference in the migration index was found between whole fetal and fetal gastrointestinal tract extracts. The migration index did not depend on CEA concentration in these fetal extracts. These results show that leucocytes from patients with gastric or colorectal cancer were sensitized to antigenic substance(s) in the fetal extracts, and suggest that gastrointestinal cancer and fetal tissue may share some common antigens.

Physiologic status of the anorectum following sphincter-saving resection for carcinoma of the rectum.

The physiologic status of the anorectum after low anterior resections or pull-through operations of the rectum was evaluated clinically and by manometric studies. It was demonstrated that the presence of a normal anal resting pressure and an anorectal reflex were important to achieve postoperative continence after sphincter-saving operations. In patients with anastomotic leaks and poor function, a marked high-pressure zone in the anal canal and an anorectal reflex were not found, but as local inflammation resulting from the anastomotic leak disappeared, these parameters returned to normal. A normal anorectal reflex was found in one of three patients after Bacon-type pull-through operations, but the remaining two showed an increase of anal canal pressure during colonic distention. These results indicate that an elevation of anal-canal pressure in response to colonic distention plays a significant role in fecal continence at the time of "a sense of urgency" if internal sphincter function is impaired.