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Surgical aspects of patients with adenocarcinoma of the stomach operated on for cure.

BACKGROUND: A retrospective study was performed to evaluate our recent results of curative gastric resections for adenocarcinoma. METHODS: Between 1979 and 1988, 187 patients fulfilled study entry criteria. This group of patients composes 64% of all patients with tumors arising distal to the gastroesophageal junction. Tumors arising in the region of the gastroesophageal junction were excluded. Patients were classified according to the American Society of Anesthesiologists physical status classification ( > or = 3, 56%) and Eastern Cooperative Oncology Group performance status ( > or = 2, 44%). Histologic characteristics were re-reviewed. INTERVENTIONS: Subtotal and total gastrectomies were performed in 78% and 22% of the patients, respectively. Extended lymph node dissections were performed selectively (5%). Adjuvant chemotherapy and radiotherapy were employed in 3% and 2% of patients, respectively. RESULTS: Postoperative morbidity and mortality were 27% and 4%, respectively. Synchronous splenectomy (P = .06) and type of gastric resection (P = .06) showed a borderline association with postoperative complications, but did not affect postoperative mortality. With a median follow-up time of 47 months in all patients, and a median of 9 years in patients still alive, the 5- and 10-year overall survival rates (Kaplan-Meier method) were 48% and 32%, respectively. In univariate survival analysis, age, American Society of Anesthesiologists classification, stage, tumor diameter, serosal extension of tumor lymph node metastases, and type of resection showed prognostic significance. In the Cox multivariate analysis, however, only serosal extension of tumor (P < .001) and lymph node metastases (P = .02) were independent prognostic factors. CONCLUSIONS: Despite the older age and comorbid conditions of patients with gastric cancer, 5-year survival was achieved in half the patients by standard radical operations. Until appropriate controlled prospective studies are performed, total gastrectomy, splenectomy, and extended lymph node dissection should not be routinely adopted, given their unproven efficacy and potentially increased morbidity and mortality.

Adenocarcinoma↗

Expression profile of telomerase subunits in human pleural mesothelioma.

Using the TRAP assay, telomerase activity was previously detected in over 90% of human pleural mesotheliomas (MMs), but not in mesothelial cell cultures (MCCs), suggesting that telomerase re-activation occurs during multi-step mesothelioma carcinogenesis. The present study determined the expression of the telomerase RNA template (hTERC), the telomerase-associated protein (hTEP1), and the telomerase catalytic sub-unit (hTERT), in 16 pleural MMs and 4 MM-derived cell lines, in two pleural solitary fibrous tumours and in six MCCs. Reverse transcription-polymerase chain reaction analysis revealed that hTERT mRNA expression parallels the activity status documented by the TRAP assay, whereas hTERC and hTEP1 mRNA are commonly expressed in all malignant and non-malignant serosal cells and tissues. Three alternatively spliced hTERT transcripts were detected in all telomerase-positive samples, whereas neither variant could be detected in the MCCs. Detection of the hTERT protein with a commercially available antibody was not successful. These results indicate that hTERT expression is rate-limiting for human telomerase activity and that re-activation, rather than up-regulation, of hTERT expression can play a critical role in MM carcinogenesis. While waiting suitable anti-hTERT antibodies, these results provide information for the design of hTERT mRNA-specific in situ probes to study telomerase in archived pre-malignant serosal lesions.

Blotting, Western↗

Na(+) and Cl(-) transport by the urinary bladder of the freshwater rainbow trout (Oncorhynchus mykiss).

Freshwater (FW) rainbow trout (Oncorhynchus mykiss) urinary bladders mounted in vitro under symmetrical saline conditions displayed electroneutral active absorption of Na(+) and Cl(-) from the mucosal side; the transepithelial potential (V(t)) was 0.1 mV, and the short-circuit current was less than 1 microA cm(-2). Removal of Na(+) from mucosal saline decreased Cl(-) absorption by 56% and removal of Cl(-) decreased Na(+) absorption by 69%. However, active net absorption of both Na(+) and Cl(-) was not abolished when Cl(-) or Na(+) was replaced with an impermeant ion (gluconate or choline, respectively). Under physiological conditions with artificial urine (¿Na(+) = 2.12 mM, ¿Cl(-) = 3.51 mM) bathing the mucosal surface and saline bathing the serosal surface, transepithelial potential (V(t)) increased to a serosal positive approximately +7.6 mV. Unidirectional influx rates of both Na(+) and Cl(-) were 10-20-fold lower but active absorption of both ions still occurred according to the Ussing flux ratio criterion. Replacement of Na(+) with choline, or Cl(-) with gluconate, in the mucosal artificial urine yielded no change in unidirectional influx of Cl(-) or Na(+), respectively. However, kinetic analyses indicated a decrease in maximum Na(+) transport rate (J(max)) of 66% with no change in affinity (K(m)) in the low Cl(-) mucosal solution relative to the control solution. Similarly, there was a 79% decrease in J(max) values for Cl(-), again with no change in K(m), in the low-Na(+) mucosal bathing. The mucosal addition of DIDS, amiloride or bumetanide (10(-4) M) had no effect on either Na(+) or Cl(-) transport, under either symmetrical saline or artificial urine/saline conditions. Addition of the three drugs simultaneously (10(-4) M), or chlorothiazide (10(-3) M), under symmetrical saline conditions also had no effect on Na(+) or Cl(-) transport rates. Cyanide (10(-3) M) addition to mucosal artificial urine caused a slowly developing decrease of Na(+) influx to 59% and Cl(-) influx to 50% in the period after drug addition. Na(+) and Cl(-) reabsorption appears to be a partially coupled process in the urinary bladder of O. mykiss; transport mechanisms are both dependent upon and independent of the other ion.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

Factors related to survival following resection for gastric carcinoma: analysis of 903 cases.

This report is based on 903 patients with resections for gastric carcinoma between October 1957, and July 1969, entered in controlled trials of adjuvant therapy with Thio-TEPA and FUDR. Neither Thio-TEPA nor FUDR, as administered, prolonged survival. The extent of disease at the time of curative surgery is related to survival for the first 36 months postoperatively. Involvement of lymph nodes, resection of the esophagus, and serosal penetration are predictive of recurrence up to 36 months. There appear to be three groups of patients: 1) Cured (26%); 2) Slowly growing tumor--23% (median survival, 25 months); and 3) Rapidly growing tumor--51% (median survival, eight months). The absence of blood-vessel invasion, lymphatic invasion, lymph-node involvement, and serosal penetration characterize those patients in Group A.

Adult↗

Intraperitoneal free cancer cells and their viability in gastric cancer.

Free cancer cells in the peritoneal cavity of 100 patients with gastric cancer were examined by means of Douglas lavage, and their viability was estimated by 3H-thymidine uptake with autoradiographical technic. Furthermore, the effect of mitomycin-C on the viability of free cancer cells in the peritoneal cavity was studied. The appearance of intraperitoneal free cancer cells was dependent on the degree of invasion of cancer to the gastric serosa; that is, free cancer cells were not found in cases without serosal invasion, but were found in 48% with serosal invasion. The viability of free cancer cells in the peritoneal cavity was relatively high, but could be suppressed remarkably by intraperitoneal administration of 10 mg of mitomycin-C.

Ascitic Fluid↗

Expression of c-erbB-2 oncoprotein in gastric carcinoma. Immunoreactivity for c-erbB-2 protein is an independent indicator of poor short-term prognosis in patients with gastric carcinoma.

Correlations of c-erbB-2 protein expression with clinical outcomes of gastric carcinomas were studied in 189 gastric carcinomas. There were 23 (12.2%) carcinomas with evidence of c-erbB-2 protein in which the reaction was localized to the cell membrane. There was no significant association between c-erbB-2 staining and the macroscopic or histologic type of the carcinomas. c-erbB-2-stained tumors were more likely to be associated with serosal invasion, nodal involvement, and peritoneal metastasis, than c-erbB-2-unstained ones. In addition, c-erbB-2 was stained in none of early gastric carcinomas. The 5-year survival rates of the c-erbB-2 protein-positive and the protein-negative group were 11% and 50%, respectively. When the c-erbB-2 tissue status and seven clinicopathologic variables as conventional prognostic factors were entered simultaneously into the Cox regression model, serosal invasion, hepatic metastasis, peritoneal metastasis, nodal status, and c-erbB-2 tissue status emerged as independent prognostic variables. The results suggested that c-erbB-2 protein expression might be enhanced in advanced stages during the progression of gastric carcinoma. In this particular group of patients, immunoreactivity for c-erbB-2 protein is an indicator of poor short-term prognosis.

Adult↗

Carcinoembryonic antigen levels in peritoneal washings can predict peritoneal recurrence after curative resection of gastric cancer.

Carcinoembryonic antigen (CEA) levels were determined in the peritoneal washings from 120 patients with gastric cancer and 9 patients with benign diseases. Elevated values (greater than 100 ng/g of protein) were observed in 20 of 25 patients with gastric cancer with visible dissemination and 16 of 25 patients with serosal invasion but no dissemination. The same elevation was found in only 9 of 70 patients with no serosal invasion and none of the patients with benign disease. The 2-year survival rates after curative operation for the patients with and without elevation of CEA levels were 21% (19 patients) and 100% (66 patients), respectively (P less than 0.001). A negative correlation was found between CEA levels and survival times after noncurative operation. These results indicate that the CEA level in peritoneal washings could be a sensitive detector of invisible peritoneal dissemination and a new predictor for the postoperative prognosis of gastric cancer.

Carcinoembryonic Antigen↗

Diagnostic factors in gastric cardia cancer invading the esophagus.

BACKGROUND: The prognosis of patients with tumors in the upper one-third of the stomach, particularly those with esophageal invasion, is poor. METHODS: This study involved 168 patients with advanced cancer in the upper third of the stomach whose lesion had had invaded the esophagus. Clinical and pathologic studies were performed with respect to diagnostic factors and histologic differentiation of the lesion. RESULTS: Eighty-three patients (49.4%) had differentiated gastric cancer, and 85 (50.6%) had undifferentiated cancer. The survival time was shorter for patients with undifferentiated cancer than for those with differentiated cancer (P < 0.01). Multivariate analysis showed operative curability, liver metastasis, peritoneal dissemination, lymph node metastasis, serosal invasion, and tumor size to be independent prognostic factors. In patients with undifferentiated cancer, tumors were larger, serosal invasion was prominent, lymph node metastasis was present in 85.9% of cases, 64.7% of metastases were noncuratively resected, and survival time was less favorable. CONCLUSIONS: Our analysis shows that a group of patients at increased risk for tumor advancement will benefit from more aggressive therapy.

Adult↗

E-cadherin and urokinase-type plasminogen activator tissue status in gastric carcinoma.

BACKGROUND: E-cadherin (ECD) is known to be an invasion suppressor gene, and urokinase-type plasminogen activator (uPA) plays a central role in infiltration of solid cancers. METHODS: To elucidate the relationship between expression of these factors and metastasis in patients with gastric cancer, the authors examined immunohistochemically a combination analysis of uPA and E-cadherin expression in 98 primary tumors, and the results were correlated with several parameters related to metastasis. RESULTS: Among 125 tumors, 42 (34%) were evaluated as having E-cadherin expression (E-cadherin-positive), and the other 83 (66%) were defined as having reduced E-cadherin expression (E-cadherin-negative). uPA immunoreactivity was observed in 82 tumors (66%). There were four subtypes of patterns of uPA and E-cadherin expression: 22 uPA-negative/E-cadherin-positive, 17 uPA-negative/E-cadherin-negative, 21 uPA-positive/E-cadherin-positive, and 65 uPA-positive/E-cadherin-negative, uPA overexpression and reduced E-cadherin expression were associated with lymph node metastasis, vessel invasion, serosal involvement, and poor prognosis. In addition, uPA-positive/E-cadherin-negative tumors were associated significantly with large tumors, positive serosal invasion, lymph node involvement, and poor prognosis. Patients with uPA-positive/E-cadherin-negative expression had the poorest prognoses, compared with the three other groups of patients uPA-positive/E-cadherin-negative tumors had a fourfold relative risk of death when compared with uPA-negative/E-cadherin-positive tumors. A Cox proportional hazard model projected lymph node status as the strongest of the prognostic variables followed by DNA ploidy patterns and uPA/E-cadherin tissue status. CONCLUSIONS: These results indicate that immunohistochemical combination analysis of uPA and E-cadherin expression may be a powerful aid in evaluating metastatic potential or the prognosis of patients with gastric cancer.

Adult↗

A comparative study of the clinical manifestations of systemic lupus erythematosus in Caucasians in Rochester, Minnesota, and Chinese in Singapore, from 1980 to 1992.

OBJECTIVE: To examine the relationship between ethnicity and major organ involvement at and after diagnosis in community-based cohorts of Caucasian and Chinese systemic lupus erythematosus (SLE) patients resident in Rochester, Minnesota, and Singapore, respectively. METHODS: Clinical manifestations at and after diagnosis were compared in Caucasian and Chinese SLE patients. The association between ethnicity and disease manifestations at and after diagnosis was determined using logistic regression and Cox proportional hazards models, respectively, adjusting for the influence of demographic, socioeconomic, disease-related, and therapy-related factors. RESULTS: At diagnosis, Caucasian SLE patients were 3 times more likely than Chinese SLE patients to have serositis (odds ratio [OR] 3.11, 95% confidence interval [CI] 1.01-9.71), nearly 7 times more likely to have a hematologic disorder (OR 6.95, 95% CI 2.20-21.97), and far less likely to have a malar rash (OR 0.19, 95% CI 0.07-0.54) or positive antinuclear antibodies (OR 0.11, 95% CI 0.03-0.52). Ethnicity was not associated with the prevalence of proteinuria or central nervous system (CSN) and other major organ involvement at diagnosis. After diagnosis, there was a trend toward less development of proteinuria and other major organ involvement in Caucasians (relative risk [RR] 0.47, 95% CI 0.19-1.15, and RR 0.22, 95% CI 0.05-1.04, respectively). CONCLUSION: Chinese SLE patients are far less likely to have serositis or a hematologic disorder at diagnosis and may be more likely to develop proteinuria or CNS or other major organ involvement over the course of the disease, compared with Caucasian SLE patients. This may contribute to the increased mortality seen in Chinese SLE patients.

Adolescent↗

A new method for the assessment of gut viability.

A surface polarographic oxygen electrode was modified so that on the basis of physical considerations its reading became dependent on blood flow. The preliminary results show that when applied to the serosal surface of the bowel under operative conditions, readings correlated well with total blood flow to the segment measured by electromagnetic flowmetry. Graded local ischaemic areas could also be detected. Readings from the serosal surface appeared to be independent of those from the mucosa. The instrument may therefore provide a useful surgical tool for detecting partially ischaemic areas of bowel.

Animals↗

Exfoliated cells and in vitro growth in colorectal cancer.

Cells exfoliated from colorectal cancers may only be implicated in local recurrence if they are proven to be viable and capable of growth. Thirty patients with primary colorectal cancer were studied. Cells were obtained from primary tumour, uninvolved mucosa, mesorectum, lumen of the bowel, luminal mucus, serosal surface of the bowel and from washings of the tumour bed after dissection. Colonies grew in vitro in monolayer culture from 21/30 primary tumours; 11/41 mesorectum specimens; 11/27 luminal washings; 14/29 luminal mucus specimens; 1/27 serosal surface washings and 3/13 post-dissection washes. Colonies stained positively for the epithelial markers cytokeratin and desmosomes and also for carcinoembryonic antigen. Cells capable of in vitro growth are present in these various sites and, if spilled at operation, may well be implicated as one of the factors leading to local recurrence.

Adult↗

Operative findings in patients with early forms of gallbladder cancer.

Of 52 patients diagnosed as having gallbladder cancer in a 2-year period, 15 had no evidence of serosal involvement. Four of these 15 patients had tumour confined to the mucosa and did not undergo reoperation while 11 patients underwent lymph node dissection and hepatic wedge resection at a second operation. The correct diagnosis was suspected before the first operation in only one of 11 patients undergoing reoperation; the tumour was found microscopically in seven patients. Of the 11 patients who underwent reoperation, five had lymph node involvement, and three of these patients had both liver and lymphatic involvement. Our results underline the difficulty of establishing the diagnosis of gallbladder cancer before operation and the lack of major morbidity and mortality suggests that there may be value in reoperating on patients found to have gallbladder carcinoma without serosal involvement. Further follow-up is required to assess the long-term value of this approach.

Adult↗

Prognostic significance of regional lymph node reaction after curative resection of advanced gastric cancer.

The prognosis of patients with advanced gastric cancer who undergo curative resection is still unsatisfactory. The relationship between prognosis and various factors such as stage, lymph node metastasis, serosal invasion and regional lymph node reaction (follicular hyperplasia and sinus histiocytosis) was evaluated. Of the factors studied, the only one that correlated well with survival was sinus histiocytosis. Lymph node metastasis was related weakly to prognosis. No correlation between prognosis and stage, serosal invasion or follicular hyperplasia was observed. Sinus histiocytosis may represent the morphological tumour-host immune reaction. Lymph node metastases or histological types were not related to regional lymph node reaction. These results suggest that sinus histiocytosis could be a useful prognostic factor for gastric cancer. Intensive postoperative follow-up for recurrence may be necessary even for patients with low-grade sinus histiocytosis in whom curative surgery is attempted.

Adenocarcinoma↗

Hepatic resection for metastatic tumours from gastric cancer: analysis of prognostic factors.

Determinants of prognosis after hepatic resection for metastasis from gastric cancer were studied in a retrospective series of 21 patients, including four who survived more than 5 years after surgery. All patients underwent apparently curative resection. Synchronous or metachronous resection, age, sex, histological type, depth of invasion, lymphatic and venous invasion, lymph node involvement and number of hepatic metastases were analysed as prognostic factors for survival. Serosal invasion was the only significant determinant at synchronous resection. Both lymphatic and venous invasion were significant prognostic factors available after histological examination. Combined analysis of these two histological variables revealed that patients positive for both were at a significantly higher risk for both overall and disease-free survival. It is suggested that hepatic resection should be attempted in patients with synchronous or metachronous metastases if there is no serosal invasion by the primary gastric tumour, and if the primary tumour has neither venous nor lymphatic invasion in the case of metachronous metastases.

Adult↗

Directional porosity of porcine small-intestinal submucosa.

Small-intestinal submucosa (SIS) has been shown to be a promising biomaterial for vascular graft applications. This study examines the directionality property of SIS porosity using 35 SIS specimens from 13 pigs. In addition, the effects of the weight of the donor pig, pre-conditioning of 13 additional SIS specimens, and the duration of the test of five additional SIS specimens on such porosity are reported. The porosity from serosal to mucosal direction was found to be four times greater than the porosity in the opposite direction. The weight of the donor pig was not found to be an important factor in SIS porosity. Preconditioning served to increase the average serosal porosity index at 120 mm Hg static water pressure from 2.99 to 8.33 mL/(min cm2). The porosity in the mucosal direction was not affected by preconditioning. Porosity in both directions decreased with increasing test duration. The directionality property of SIS porosity may be an important factor in its success as a vascular graft. The term 'porosity' is used throughout this article, but current standards also refer to the term 'permeability' to describe the passage of liquid through a vascular graft.

Animals↗

Ultrasonographic diagnosis of submucosal tumors of the stomach: the "bridging layers" sign.

The ultrasonic findings in 14 cases with submucosal tumors and one case with extragastric lymphoma using the fluid-filled stomach method were reviewed to determine the appearance of the stomach wall in submucosal tumors. Two characteristic ultrasound features of submucosal tumors were demonstrated in all 14 lesions except in two located high in the fundus of the stomach. One feature was mucosal bridging layers, i.e., three layers could be seen on the mucosal side of the tumors, and at least two of them continued to layers 1 and 2 of the normal gastric wall. The other was a serosal bridging layer, i.e., layer 5 of the normal gastric wall ran toward the serosal side of the tumor. On the basis of a "bridging layers" sign, we believe a definite diagnosis of submucosal tumor can be obtained from ultrasound images.

Diagnosis, Differential↗

The role of K+ and Cl- conductances in chloride secretion by the opercular epithelium.

The opercular epithelium of the teleost Fundulus heteroclitus, when mounted in a lucite chamber under short-circuited conditions, secretes Cl- at a rate equivalent to the short-circuit current (Isc). The transepithelial Na+ movements are passive and proceed by a paracellular pathway. The addition of 2 X 10(-3) M Ba2+ to the serosal bathing solution inhibited the Isc 76.8% with no effect on the transepithelial conductance (Gt). The addition of 5 X 10(-4) M Cu2+ to the mucosal bathing solution inhibited the Isc 79.6% and reduced the Gt 35.6%. These inhibitory effects of Ba2+ and Cu2+ on the Isc were initiated within 1 minute after exposure with maximum effects occurring within 20 and 30 minutes, respectively. Simultaneous 36Cl- and 22Na+ unidirectional fluxes were performed on paired epithelia from the same fish. Serosal Ba2+ and mucosal Cu2+ inhibited the Cl- secretory flux 30.2 and 58.9%, respectively. The resulting net Cl- flux after inhibition was not significantly different from the mean measured Isc. Neither ion had significant effects on the Cl- influx (mucosa to serosa) or the unidirectional Na fluxes. These results indicated that the effects of both Ba2+ and Cu2+ were most likely exclusive to the transcellular Cl- pathway. Ba2+ is proposed to inhibit Cl- secretion by blocking the basolateral K+ channels, depolarizing the cell, and reducing the electrochemical driving force for Cl- across the apical membrane. Cu2+ is proposed to inhibit Cl- secretion by blocking the apical membrane Cl- channels.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗