Tuberculosis of the esophagus.

We report a case of a patient with esophageal tuberculosis, a very uncommon form of extrapulrhonar tuberculosis. Initially, because of constitutional symptomatology and radiological findings of mediastinal lymph node enlargement, lymphoma was considered. However, the endoscopic findings of ulcerative masses and a sinus tract revealed by esophagram were suspicious of tuberculous origin. Diagnosis was achieved after bacterial examination of smear samples from esophageal ulcers that revealed bacillus tuberculous and histological demonstration of caseating granulomas in cervical lymph nodes. Tuberculous mediastinal lymphadenitis was thought to be source of the spread to esophagus.The patient was successfully treated with a three antituberculous drugs regimen. In spite of its rarity, even in patients without risk factors, the diagnosis would be considered in the differential diagnosis of uncertain esophageal lesions.

Genetic alterations of candidate tumor suppressor ING1 in human esophageal squamous cell cancer.

Overexpression of ING1, a candidate tumor suppressor gene, efficiently blocks cell growth or induces apoptosis in different experimental systems. ING1 maps to chromosome 13q33-34, and because loss of the terminal region of chromosome 13q has been implicated in esophageal squamous cell cancer (ESCC), we examined ESCC for genetic alterations of ING1. Among 31 informative cases of ESCC, 58.9% of the tumors showed allelic loss at chromosome 13q33-34, and we detected four tumor-specific missense nucleotide changes. These alterations were found within the PHD finger domain and nuclear localization motif of the ING1 and may be functionally involved in the development of ESCC. Because immunohistochemical study revealed that all of the ESCC samples showed loss of ING1 protein expression, genetic or epigenetic alterations that abrogate the normal function of ING1 may contribute to esophageal squamous cell carcinogenesis.

Antisense-mediated suppression of human heparanase gene expression inhibits pleural dissemination of human cancer cells.

Heparan sulfate proteoglycans is a major component of the cell surface and extracellular matrix and functions as a barrier against cationic molecules and macromolecules. Heparanase is an endoglucuronidase capable of specifically degrading heparan sulfate, and its activity is associated with the metastatic potential of tumor cells. To inhibit human heparanase expression in human cancer cells, we constructed an adenoviral vector carrying a full-length human heparanase cDNA in an antisense orientation (Ad-AS/hep). Increased heparanase expression in T.Tn human esophageal cancer cells and A549 human lung cancer cells after infection with an adenovirus vector expressing the human heparanase gene (Ad-S/hep) was specifically inhibited by simultaneous infection with Ad-AS/hep in a dose-dependent manner. A modified Boyden chamber assay demonstrated that infection with Ad-AS/hep significantly inhibited in vitro invasion of A549 cells after Ad-S/hep infection. Moreover, intrathoracic administration of Ad-AS/hep reduced the number and size of heparanase-expressing A549 tumors implanted intrathoracically into BALB/c-nu/nu mice. Our results suggest that heparanase contributes to the invasive phenotype of tumor cells, and that antisense-mediated inhibition of heparanase activity may be efficacious in the prevention of pleural dissemination.

TNF combined with IFN-alpha accelerates NF-kappaB-mediated apoptosis through enhancement of Fas expression in colon cancer cells.

Immunostaining and EMSA revealed that NF-kappaB was activated strongly by TNF/IFN-alpha compared to TNF alone in a human colon adenocarcinoma cell line, RPMI4788. Although inhibition of activated NF-kappaB, by using an NF-kappaB decoy, reduced cell viability after treatment with TNF only, NF-kappaB decoy resulted in recovery of cell viability after TNF/IFN-alpha treatment. Caspase-3 activity was increased in cells induced by TNF/IFN-alpha, while suppression of caspase-3 activity was observed in cells transfected with NF-kappaB decoy and then treated by TNF/IFN-alpha. On the other hand, Fas expression was strongly enhanced by TNF/IFN-alpha, and inhibition of TNF/IFN-alpha-induced NF-kappaB activation, by using NF-kappaB decoy, decreased Fas expression. Cell viability and caspase-3 activity decreased in cells treated with TNF/IFN-alpha and anti-FasL antibody. Taken together, our findings suggest that activated NF-kappaB induced by the crosstalk between TNF and IFN-alpha is a novel pro-apoptotic signal acting via enhancement of Fas expression.

Heparanase expression correlates with malignant potential in human colon cancer.

PURPOSE: Heparanase cleaves carbohydrate chains of heparan sulphate proteoglycans and is an important component of the extracellular matrix. This study was designed to determine the relation between heparanase expression and prognosis of patients with colon cancer. METHODS: The study included 54 patients (35 males and 19 females) who underwent colorectal resection for colorectal cancer between January 1992 and December 1994. Expression of heparanase protein and mRNA were determined and correlated with various clinicopathological parameters. In vitro studies were also performed to examine tumor invasion and to test the effects of heparanase inhibition, and in vivo studies were performed to examine tumor metastasis and prognosis. RESULTS: Heparanase expression was detected in the invasion front of the tumor in 37 of 54 (69%) colon cancer samples, whereas 17 of 54 (31%) tumors were negative. Expression of heparanase was significantly more frequent in tumors of higher TNM stage (P=0.0481), higher Dukes stage (P=0.0411), higher vascular infiltration (P=0.0146), and higher lymph vessel infiltration (P=0.0010). Heparanase expression in colon cancers correlated significantly with poor survival (P=0.0361). Heparanase-transfected colon cancer cells exhibited significant invasion compared with control-transfected colon cancer cells (P=0.001), and the peritoneal dissemination model also showed the malignant potential of heparanase-transfected cells, as assayed by number of nodules (P=0.017) and survival (P=0.0062). Inhibition of heparanase significantly reduced the invasive capacity of cancer cells (P=0.003). CONCLUSIONS: Heparanase is a marker for poor prognosis of patients with colon cancer and could be a suitable target for antitumor therapy in colon cancer.

Topological analysis of p21WAF1/CIP1 expression in esophageal squamous dysplasia.

In the normal stratified squamous epithelium of the esophagus, only the third to the fifth layers of cells express the cyclin-dependent kinase inhibitor p21WAF1/CIP1 (p21). Using immunohistochemical staining, we examined the topological distribution of cells expressing p21, p53, Ki67, and cytokeratin 10 (CK10), a differentiation marker of esophageal squamous cell carcinoma (SCC), in 25 superficial SCCs and 72 dysplastic lesions of the esophagus. Image analysis of p21, p53, and Ki67 expression was also performed in 48 dysplastic lesions. In superficial SCCs, although Ki67- and p53-expressing cells were mainly distributed in the deep layers of tumors despite tumor differentiation, the distribution of p21 correlated with tumor differentiation. In dysplastic lesions, p53- and Ki67-coexpressing cells tended to locate in the same layers and expand in the lower layers of epithelium with the progression of dysplasia. p21-expressing cells shifted to the upper layers of the epithelium with the progression of dysplasia. However, this change was heterogeneous; in some lesions, p21-expressing cells were confined to the superficial layers of atypical cells (confined type), whereas in others, p21-overexpressing cells were scattered among atypical cells (scattered type). CK10 expression was observed in 25% of dysplastic lesions, and the frequency of CK10 expression was significantly higher in the scattered than in the confined type. Our results suggest that esophageal squamous dysplasia represents the earliest pathological process in esophageal squamous carcinogenesis. Our results also suggest that differentiation of esophageal SCC is determined at the stage of dysplasia, and that p21 plays a critical role in the differentiation process.

Flow cytometric analysis on perforin induction in peripheral blood mononuclear cells with interleukin-2 or OK-432.

Perforin is a protein present in the cytoplasmic granules of killer cells and is considered to be an important effector molecule. We assessed the perforin appearance via flow cytometry in human peripheral blood mononuclear cells stimulated in vitro for 3 days by recombinant interleukin-2 (rIL-2) or OK-432, a biological response modifier. The relationship between the lymphocyte subsets and perforin was investigated via two-color assay. CD4-positive cells had almost no perforin, and most of the CD16-positive cells did. Regarding the relationship with CD8, some of the bright positive cells (which were likely T cells) and most of the dull positive cells (likely NK cells) had perforin. Mean fluorescence was greatest in perforin-positive cells incubated with rIL-2, less in cells incubated with OK-432, and minimal in cells incubated in a medium without additives. Immunohistochemical staining with antiperforin antibody revealed that blast-transformed and enlarge cells were stained positively and that the intensity of staining of each cell alone was enhanced in cells incubated with OK-432 or rIL-2. If the fluorescence intensity of perforin-positive cells correlates with the amount of perforin in those cells, then the appearance of perforin was enhanced with OK-432, more enhanced with rIL-2, and consistent for cytotoxicity against K562 and Daudi cells. IL-2 was induced by OK-432, suggesting that the indirect effect of this IL-2 may play a role in OK-432-perforin induction. The results suggest that perforin may be an effector molecule in killer cells induced by rIL-2 or OK-432.

Novel experimental models of human cancer metastasis in nude mice: lung metastasis, intraabdominal carcinomatosis with ascites, and liver metastasis.

The ability of RPMI 4788 cells, a human colon cancer cell line, to produce experimental metastases in the lung, intraperitoneal cavity, and liver was studied in nude mice. Injection of 2 X 10(6) tumor cells into the tail vein of nude mice produced metastatic lung tumors, and an intraportal injection of 5 X 10(6) cells produced metastatic liver tumors. An intraabdominal carcinomatosis with ascites was formed after an i.p. injection of 5 X 10(6) tumor cells. The nude mice with lung metastasis or intraabdominal carcinomatosis always died within a few weeks. Macroscopic observation showed that the number of lung metastatic nodules on day 21 after tumor inoculation was 311.3 +/- 78.2 (mean +/- SD) in BALB/C nude mice, and 187.5 +/- 26.7 in ICR nude mice. In survival experiments, the mice with intraabdominal carcinomatosis showed a mean survival of 29.0 +/- 1.7 (mean +/- SD) days in BALB/C nude mice and 43.6 +/- 6.1 days in ICR nude mice. These novel experimental models of metastases in nude mice produced by injection of RPMI4788 cells had high reproducibility and may be useful not only for the study of the metastatic process but also for testing anticancer drugs.

In vivo influence of p53 status on proliferation and chemoradiosensitivity in non-small-cell lung cancer.

Alteration of the p53 gene product is a frequent event in the progression of lung cancer. However, its importance to proliferation and response to chemoradiotherapy remains unclear. Thus, to assess its influence directly in vivo, we implanted into nude mice two kinds of human non-small-cell lung cancer (NSCLC) cells: H226br having a homozygous gene mutation in p53 (mt-p53) and H226b with intact p53 (wt-p53). We found that mt-p53 tumors grew substantially faster than wt-p53 tumors. Furthermore, treatment with cisplatin and radiation did not reduce the size of mt-p53 tumors, while wt-p53 tumors regressed by approximately 60%. Terminal-deoxytransferase-mediated dUTP-biotin nick-end labeling assay revealed apoptosis to be the mechanism responsible for the regression. Interestingly, apoptosis occurred in mt-p53 tumors although only at high doses of cisplatin and not at the magnitude detected in wt-p53 tumors. Cell labeling by staining with bromodeoxiuridine indicated that p53 is an important factor in modulating growth in NSCLC tumors. Our results are consistent with the notion that correction of a single genetic lesion enhances the therapeutic effect of chemotherapy.

The p53 gene is a potent determinant of chemosensitivity and radiosensitivity in gastric and colorectal cancers.

We previously reported that introduction of the wild-type p53 gene into human cancer cells with deleted p53 enhanced apoptosis induced by chemotherapy [Fujiwara et al. (1994) Cancer Res 54:2287]. This suggests that p53 status could be a potent determinant of the therapeutic efficacy of DNA-damaging cancer therapy. We analyzed 24 patients with gastric or colorectal cancer for p53 mutations and apoptotic changes in surgical specimens. Out of 11 patients with gastric cancer, 3 were treated with chemotherapeutic drugs before resection; 5 of 13 patients with colorectal cancer had 30 Gy radiation prior to surgery. p53 mutations were detected in 4 cases of gastric cancer (36.4%) and in 6 cases of colorectal cancer (46.2%) by immunohistochemical staining. The preoperative DNA-damaging therapies increased the number of apoptotic cells in wild-type-p53-expressing tumors; tumors with mutant p53, however, significantly showed fewer apoptotic cells compared with those expressing wild-type p53. The p53-inducible WAF1/CIP1 protein was immunohistochemically observed in wild-type-p53-containing tumors, whereas mutant-p53-expressing tumors expressed no detectable WAF1/CIP1. Taken together, we conclude that p53 mutations are associated with the poor response of chemotherapy and radiotherapy.

Assessment of apoptosis in oesophageal carcinoma preoperatively treated by chemotherapy and radiotherapy.

Apoptosis, programmed cell death, was immunohistochemically determined in 55 samples of oesophageal squamous cell carcinoma using the BM1 Mab. Sections from patients not treated (group 1, n = 12) or preoperatively treated by chemotherapy (group 2, n = 11), radiation (group 3, n = 13) or both (group 4, n = 8), and 11 additional cases of high-grade dysplasia or early cancer were examined. Most of the apoptotic cells were BM1-positive and checked by TUNEL proved to be nick end positive. They accounted for 7 (11%), 19 (29%), 21 (32%) and 26 (38%) cells per field in those 4 groups respectively. Chemotherapy and/or radiation significantly increased the number of apoptotic cells as compared to controls (p = 0.029 and p = 0.029, respectively). To assess the implications of the oncogene expression in the apoptotic pathway, additional section stained with bcl2 and p53 were negative for bcl2 and were positive for p53 in 16 samples (37%). Overall, positive cases for p53 mutation showed a significantly decreased incidence of apoptotic cells (p = 0.03). These results suggest that in situ assessment of apoptotic response better correlates to the apoptosis induced by radiation than that by chemotherapy, that abnormalities of the p53 protein decrease the apoptotic response in oesophageal carcinoma, and that immunohistochemical analysis of p53 protein helps to determine the sensitivity to these anticancer agents.

Anti-proliferative and cytokinetic effects of tumor necrosis factor-alpha, interferon-alpha and 5-fluorouracil on a human tumor xenograft.

We have previously reported that interferon-alpha (IFN-alpha) and tumor necrosis factor-alpha (TNF-alpha) blocked the cell cycle progression of cancer cells at the S to G2 transition, causing a synergistic antitumor effect. In this study, the combined effects of both these cytokines and 5-fluorouracil (FUra) on tumor growth and cell cycle progression were investigated in a human colon cancer cell line, RPMI 4788, transplanted in CD-1 nude mice. Daily administration of IFN-alpha and TNF-alpha for 21 days markedly suppressed the tumor growth and induced cytokinetic alterations in which S phase cells were increased and cells in G2/M phase were decreased. FUra added to these cytokines further suppressed tumor development but did not affect the cytokinetics further. Combination of FUra and cytokines in a low dose, either of which alone had no effect, suppressed the tumor growth. These findings demonstrate that IFN-alpha, TNF-alpha and FUra have a distinct antitumor effect in combination.

Anti-proliferative effect of combined tumour necrosis factor-alpha and interferon-alpha on human pancreatic cancer in vitro and in vivo.

The anti-proliferative effects of tumour necrosis factor-alpha (TNF-alpha) and interferon-alpha (IFN-alpha), alone or in combination, on human pancreatic cancer cells lines (PANC-1, MIA PaCa-2 and BxPC-3) and human pancreatic cancer tumour (Exp-58), were investigated in vitro and in vivo. The anti-proliferative effect was determined using the dye uptake method and the subcutaneous tumour model. Combined TNF-alpha and IFN-alpha demonstrated marked synergistic and/or additive effects in comparison with their effects as single agents. These results suggest that combined cytokine therapy of TNF-alpha and IFN-alpha may make possible some improvement in the treatment of pancreatic carcinoma patients in the future.

Tissue levels of chemotherapeutic agents for hepatic metastasis during hepatic arterial and portal injection.

Hepatic metastasis is one of the most important prognostic factors in digestive organ cancer, and hepatic arterial infusion is aggressively performed for therapy of nonresectable metastatic liver cancer. Although comparatively high response rates have been attained in some cases, this treatment has been ineffective in not a few cases because these metastatic tumors are frequently hypovascular in nature. To develop better methods of administering chemotherapeutic agents, we performed basic experiments concerning intraportal administration which has been regarded as having a generally negative effect, focusing on a report indicating that portal supply is dominant along the borders of metastatic liver cancer tumors. VX2 carcinoma cells were inoculated into the hepatic parenchyma beneath the capsule of juvenile Japanese white rabbits. Drugs were infused 2 weeks after the inoculation, then tissue and blood were sequentially sampled. Mitomycin C (1.7 mg/kg) was infused either by bolus injection to the hepatic artery (arterial infusion group) or by bolus injection to the portal vein (portal infusion group). Five-fluorouracil (9.5 mg/kg) and Cisplatin (1.6 mg/kg) were likewise infused continuously over 60 min, and tissue levels of the drugs were compared between the two groups. Mitomycin C and 5-fluorouracil levels were measured by HPLC and Cisplatin levels were measured by atomic absorption spectrophotometry. As a result, the levels of every drug in VX2 tumor tissue did not significantly differ between the arterial infusion group and the portal infusion group, while the levels were significantly higher than those in the intravenous infusion group. Using portal infusion, we observed a drug transition which was not inferior to that of arterial infusion, suggesting that an imported antitumoral effect may be obtained with this method compared with intravenous infusion.

In vivo augmentation of the intratumoral concentration of 5-fluorouracil by cepharanthine--a biscoclaurine alkaloid.

We have investigated the interaction between Cepharanthine (CEP), a multi-functional alkaloid that has the capacity to stabilize the cell membrane, and 5-fluorouracil (5-FU) against a human colon cancer cell line (RPMI 4788) transplanted into nude mice. Their anti-tumor effects were assessed in a group of 7 mice intravenously injected with CEP (5 mg/kg/day) and/or 5-FU (15 mg/kg/day) during a 3-week treatment. The results were compared with a control and a 5-FU group, which received saline solution and 5-FU alone, respectively. The tumors were harvested 2 h after 5-FU administration. On an additional 4 groups of 5 mice, the intratumoral concentration of 5-FU was assessed by a high performance liquid chromatographic (HPLC) method 2, 4, 6 and 12 h following CEP (5 mg/kg) injection 1 h prior to, simultaneously, and 1 h after injection of 5-FU (30 mg/kg). The mean (SD) intratumoral concentration of 5-FU was 0.16 (0.05) mu g/g, 0.32 (0.19) mu g/g, 0.32 (0.16) mu g/g and 0.21 (0.13) mu g/g in the control and the three other groups treated with CEP, respectively. This concentration was about twice as high in mice simultaneously treated with CEP compared to those treated by 5-FU alone. Relatively higher concentrations of 5-FU were noted up to 4 h following 5-FU injection in mice treated with CEP than in those injected only with 5-FU. CEP also enhanced the inhibitory effects of the 5-FU on tumor growth rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Antitumor effect of natural human tumor necrosis factor-alpha and natural human interferon-alpha in combination against human cancer transplanted into nude mice.

We studied the in vivo antitumor effects of natural human tumor necrosis factor-alpha (nHuTNF-alpha) and natural human interferon-alpha (nHuIFN-alpha), both of which were produced by HVJ (hemagglutinating virus of Japan)-stimulated acute lymphatic B cell leukemia line, BALL-1 cells. To clarify the interaction between nHuTNF-alpha and nHuIFN-alpha, we used novel experimental models of lung metastasis and intraabdominal carcinomatosis which we developed in nude mice using a human tumor line, RPMI 4788. While the intravenous administration of nHuTNF-alpha or nHuIFN-alpha alone inhibited lung metastasis, the two cytokines given in combination synergistically inhibited lung metastasis. In a comparative study, nHuTNF-alpha and recombinant human interferon-gamma (rHuIFN-gamma) in combination also synergistically inhibited lung metastasis. Treatment with nHuTNF-alpha and nHuIFN-alpha combined significantly prolonged the survival of nude mice with intraabdominal carcinomatosis. Complete regression of five different human tumor xenografts was achieved by the simultaneous intratumoral injection of nHuTNF-alpha and nHuIFN-alpha. Histological examination revealed that tumor cell lysis occurred 24 h after the intratumoral administration of the cytokines. No significant signs of toxicity to nude mice were observed at any dose tested. The synergism of nHuTNF-alpha and nHuIFN-alpha may allow treatment at a relatively low dose range, thus minimizing side effects. The wide range of anticancer activity of these agents may provide better therapeutic efficacy. The in vivo assay systems which we have developed are useful for the analysis of the biological activities and interactions of cytokines and chemotherapeutic drugs.

Antitumor effect of combined intraperitoneal administration of human recombinant interferon-beta and interferon-gamma against intraabdominal carcinomatosis in nude mice.

The development of useful therapy for intraabdominal carcinomatosis originating from gastrointestinal cancer is an important theme in cancer therapy. We developed recently an experimental model of intraabdominal carcinomatosis in nude mice by intraperitoneal transplantation of human colon cancer cells (RPMI 4788). Using this model, we investigated the antitumor effects of recombinant human interferon (rIFN)-beta and rIFN-gamma administered singly or in combination. Treatment was initiated 2 days after CD-1 nude mice were inoculated intraperitoneally with 5 X 10(6) RPMI 4788 cells. Intraperitoneal administration for 10 consecutive days of either rIFN-beta (2.5 X 10(5) IU/mouse/day) or rIFN-gamma (2.5 X 10(5) JRU/mouse/day) resulted in a significant prolongation of survival compared with the saline control group [survival in the control: 41.8 +/- 5.6 days (mean +/- SD)]. Combined administration of rIFN-beta and rIFN-gamma for 10 days yielded a marked synergistic effect on the prolongation of survival (114.0 +/- 8.2 days). However, combined administration of rIFN-beta and rIFN-gamma in a single dose equal to the total dose given fractionally over 10 days did not yield a synergistic effect. These results suggest that daily administration of rIFN-beta and rIFN-gamma combined may provide a highly potent antitumor effect against human peritoneal carcinomatosis.

Synergistic effect of tumor necrosis factor-alpha and interferon-alpha on the induction of apoptosis detected by BM-1/JIMRO: a new marker of apoptosis.

The effects of the combination of natural human tumor necrosis factor-alpha (nHuTNF-alpha) and natural human interferon-alpha (nHuIFN-alpha) on the induction of apoptosis were investigated by immunohistochemical analysis with BM-1/JIMRO monoclonal antibody in RPMI 4788 tumor cells. Few tumor cells in the control culture could spontaneously undergo apoptosis. The number of positive cells increased at 2 and 4 h after treatment with nHuTNF-alpha (1 x 10(5) U/ml) and nHulFN-alpha (1 x 10(5) IU/ml). This effect was clearly maintained from 8 h up to 72 h of culture. The number of apoptotic cells also greatly increased with doses, suggesting that the apoptosis induced by nHuTNF-alpha and nHuIFN-alpha in combination was dose-dependent. nHuTNF-alpha or nHuIFN-alpha alone could induce apoptosis, but the induction increased significantly when the two cytokines were combined. These findings indicate that by combining nHuTNF-alpha and nHuIFN-alpha apoptosis can be synergistically induced in RPMI 4788 tumor cells, and may have specific therapeutic implications for clinical treatments using these two cytokines.

Antiproliferative effects of suramin on human cancer cells in vitro and in vivo.

The present experiment was undertaken to study what types of human cancers are responsive to the antiproliferative effects of suramin. The human malignant cells used were as follows: cervical cancer (HeLa), mammary cancer (MCF-7), bladder cancer (EJ), hepatoma (HuH-7, PLC/PRF/5), embryonal carcinoma (PA-1), in vitro transformed fibroblasts (KMST-6, SUSM-1, VA-13), five myeloma cell lines (KMM-1, KMS-5, KMS-11, KMS-12, RPMI 8226), Burkitt's lymphoma (Raji), acute promyelocytic leukemia (HL-60), chronic myelocytic leukemia (K562), Epstein-Barr virus nuclear antigen positive lymphoblastoid cells (KMS-9). The cells were treated with 25 to 100 micrograms/ml suramin for 72h. Proliferation of HuH-7 and two human myeloma cells (KMS-11 and KMS-12) was remarkably inhibited, and that of PA-1, PLC/PRF/5, KMST-6, two other myeloma cell lines (KMM-1 and KMS-5), Raji and HL-60, was moderately inhibited. In order to confirm part of the results obtained from in vitro experiments, in vivo experiments were also undertaken. The growth of HuH-7 cells transplanted subcutaneously into nude mice was significantly suppressed by intravenous injection of suramin. We discussed the possibility that certain types of human cancers, the growth of which seemed to be more or less dependent on polypeptide growth factors, might be sensitive to the antiproliferative effects of suramin.

Postoperative gastric motility, secretory function, and pre- and postoperative carbohydrate metabolic states in esophageal cancer patients.

This study was undertaken to assess postoperative gastric motility and gastric acid secretion, and pre- and postoperative carbohydrate metabolism in patients with esophageal cancer. The gastric motility was compared among 3 different reconstruction routes in 26 patients who were divided into 2 groups according to the duration of postoperative follow-up; group A, 3 months or less; and group B, 18 months or more. The routes used for subtotal resection of the stomach were the posterior mediastinal, retrosternal, and subcutaneous routes. All patients showed positive resting pressure in the esophagus, but peristaltic waves did not reach the gastric tube at dry swallowing in any patients and peristaltic waves appeared after eating pudding only in 1 patient in group B. The resting pressure and gastric emptying time were similar among reconstruction routes, but the incidence and amplitude of metoclopramide (MCP)-induced peristaltic waves were significantly higher in group B than in group A. Furthermore, 24-h intragastric pH monitoring of gastric secretion in a group of 9 patients revealed individual variation in gastric secretion. Some patients showed high acidity soon after operation, suggesting the need for prophylactic treatment for preventing gastric ulcer. Postoperatively, postprandial serum gastrin levels were significantly higher than preoperative levels. In the other group of 11 patients tested, preoperative and postoperative carbohydrate metabolism were not significantly different. Postoperatively, carbohydrate metabolism recovered to preoperative levels after a transient decrease. These results demonstrated that postoperative motility improved over time although no difference was found among the 3 reconstruction routes used.