Outcomes after emergency surgery for gastric perforation or severe bleeding in patients with gastric cancer

BACKGROUND AND OBJECTIVES: Free perforation and major bleeding in patients with gastric cancer are rare but serious conditions with potentially dangerous effects. To clarify the clinicopathologic characteristics of patients with these conditions and to determine the optimum management, we reviewed 16 cases of perforation and 13 cases of major bleeding in patients with gastric cancer who required emergency surgery. METHODS: We compared the clinical and histologic features of the patients with perforation and those with bleeding. Cox's multivariate regression analysis was used to compare survival rates between patients who underwent single-step surgery or a two-step radical procedure, between patients with stage I or II and stage III or IV cancer, between patients who underwent complete (R0) and incomplete (R1 or R2) resection, and between patients with bleeding and those with perforation. RESULTS: Many of the patients had advanced disease. There were no significant differences in clinicopathologic findings or survival between patients with gastric perforation and those with major bleeding. Patients who had major bleeding tended to have larger cancers. In the univariate analysis, gastrectomy (vs. no gastrectomy), R0 (vs. R1 or R2) resection, and lower stage (vs. higher stage) were highly correlated with improved survival time. CONCLUSIONS: Overall, patients with gastric cancers who underwent emergency gastrectomy had a poor prognosis, but it was better than that of patients who could not have gastrectomy because of the prXesence of advanced cancer. However, the survival rate was excellent in patients with early-stage cancer who underwent complete (R0) resection. We recommend complete resection when possible.     

Management of perforated gastric carcinoma: a report of 16 cases and review of world literature

Perforated gastric carcinoma is rare; however, it is a serious condition associated with complications. To understand the proper management of this disease and to characterize its clinical course we reviewed available data on 16 patients with perforated gastric carcinoma. We collected data on the age and sex of the patients as well as operative findings and histological features of the primary tumor. The depth of invasion and presence of lymph node metastasis were also recorded. The Union Internationale Contre Cancer stage, extent of resection, and surgical method used were reviewed. We also reviewed published information on the management of perforated gastric carcinoma. The carcinoma was stage I in three cases, stage II in one case, stage III in three cases, and stage IV in nine cases. Many patients had distant metastases. Fourteen patients underwent gastrectomy. Two patients whose preoperative condition was poor died of surgery-related complications, but patients with early-stage carcinoma underwent an R0 resection (resection of the primary tumor with negative margins) and had minimal complications. We conclude that the outcome of patients who were able to undergo radical surgery was good and correlated with the stage of cancer. It is important to perform gastrectomy rather than repair the perforation first, and a proper lymphadenectomy should follow--thus a two-step surgery when necessary.     

Hedgehog: an attribute to tumor regrowth after chemoradiotherapy and a target to improve radiation response.

PURPOSE: Despite aggressive chemotherapy, radiotherapy, surgery, or combination approaches, the survival rate of patients with esophageal cancer remains poor. Recent studies have suggested that constitutive activation of the Hedgehog (Hh) pathway in cancers of the digestive tract may contribute to the growth and maintenance of cancer. However, the relationship between Hh signaling and therapeutic response is unknown. EXPERIMENTAL DESIGN: The expression and temporal kinetics of Hh signaling and proliferation biomarkers after chemoradiotherapy were examined in esophageal tumor xenografts. Additionally, immunohistochemical analysis of Sonic Hh (Shh) and Gli-1 expression were done on residual tumors from patients who received neoadjuvant chemoradiotherapy followed by surgery. The ability of Shh signaling to induce proliferation in esophageal cell lines was determined. Expression of cell cycle checkpoint proteins was analyzed in cells in which Hh signaling was activated or inhibited. We further determined the effect of inhibiting Hh signaling in sensitizing esophageal tumors to radiation. RESULTS: We showed that the Shh signaling pathway was extensively activated in esophageal cancer xenografts and residual tumors after chemoradiotherapy and the temporal kinetics of Hh signaling preceded increases in proliferation biomarker expression and tumor size during tumor regrowth. We further showed that Hh pathway activity influences proliferation rates of esophageal cancer cell lines through up-regulation of the G1-cyclin-Rb axis. Additionally, we found that blocking Hh signaling enhanced radiation cytotoxicity of esophageal cancer cells. CONCLUSIONS: These results suggest that activation of the Hh pathway may promote tumor repopulation after chemoradiotherapy and contribute to chemoradiation resistance in esophageal cancers.     

Expression of annexin A1 in esophageal and esophagogastric junction adenocarcinomas: association with poor outcome.

PURPOSE: Annexin A1 (ANXA1) is a calcium-binding protein involved in arachidonic acid metabolism and epidermal growth factor receptor tyrosine kinase pathway. ANXA1 has been implicated in early squamous cell carcinogenesis of esophagus and correlates with degree of tumor differentiation. However, the role of ANXA1 in esophageal adenocarcinoma is unclear. Our goal was to evaluate ANXA1 expression and determine its prognostic significance in adenocarcinoma of the esophagus and esophagogastric junction. EXPERIMENTAL DESIGN: This study included 104 consecutive patients with primary resected esophageal and esophagogastric junction adenocarcinomas (11 stage I, 24 stage II, 53 stage III, and 16 stage IV). ANXA1 protein expression in each tumor was assessed by immunohistochemical staining of tissue microarrays. ANAX1 expression level was classified as high (>/=25% of tumor cells with cytoplasmic staining), low (<25% of tumor cells with cytoplasmic staining), or negative; and was correlated with clinicopathologic features and patients' outcomes. RESULTS: High ANXA1 expression was present in 39% (41 of 104) of tumors and was associated with higher pathologic T stage (P = 0.03) and distant metastasis (P = 0.04). High ANXA1 expression correlated with increased recurrence rate (P = 0.004) and decreased overall survival (P = 0.003) in univariate analysis. In multivariate analysis, ANXA1 expression and pN stage significantly correlated with recurrence rate (P = 0.008 and P < 0.001, respectively) and overall survival (P = 0.02 and P < 0.001, respectively) independent of T stage. CONCLUSION: Our results indicate that high ANXA1 expression is frequent in esophageal and esophagogastric junction adenocarcinomas, correlates with more advanced pathologic T stage and the presence of distant metastasis, and is an independent prognostic factor for patient survival.     

Low imperforate anus associated with seminal vesicle cyst,posterior urethral valve,and lung hypoplasia

This report describes the association of a low imperforate anus with a seminal vesicle cyst, posterior urethral valve, and lung hypoplasia complicated by necrotizing enterocolitis and unilateral vesicoureteral reflux. The embryological basis, diagnosis, and management of these anomalies is reviewed.     

Radiological aspects of the fetal alcohol syndrome

The fetal alcohol syndrome has recently been clinically recognised and has a characteristic facial phenotype. The condition is the result of chronic maternal alcohol ingestion affecting the first trimester. A survey of our cases has shown that skeletal maldevelopment is a part of the syndrome and can help in its early recognition.This paper was given at the 18th E.S.P.R. meeting in Oslo on 22nd May 1981     

Visinin-like protein-1 is a potent inhibitor of cell adhesion and migration in squamous carcinoma cells

Tumor cell invasion is a highly integrated and complex process comprising several biologically distinct functions such as cell adhesion, motility, proteolysis, etc. Visinin-like protein-1 (VILIP-1), a member of the neuronal EF-hand calcium-sensor protein family, plays a role in regulating tumor cell invasiveness of mouse squamous cell carcinoma (SCC). VILIP-1 enhances cyclic adenosine monophosphate levels through PKA induction. However, the mechanism by which VILIP-1 reduces cell invasiveness is not well understood. In this study, we show that VILIP-1 decreased cell adhesion and migration/invasiveness of highly invasive mouse SCC cells. Forced expression of VILIP-1 reduced cell adhesion to fibronectin in parallel to downregulating alphav and alpha5 integrin subunit levels. VILIP-1 overexpression also led to decreased migration ability. Conversely, short hairpin RNA-mediated VILIP-1 knock-down of SCC cells' characterized by little or no invasiveness, correlated with increased adhesion to fibronectin and enhanced expression of alphav and alpha5 integrin subunits together with increased cell migration. Function-blocking assays with inhibitory anti-alpha5 and anti-alphav integrin antibodies showed that both subunits contributed to cell adhesion, migration, and invasiveness of highly invasive SCC cell lines. These results point to a critical role of VILIP-1 in regulating cell adhesion and migration by downregulation of fibronectin receptor expression. Decreased or absent VILIP-1 expression in SCC cell subpopulations may lead to a more advanced malignant phenotype characterized by changes in adhesive ability and increased cell motility, suggestive of a tumor suppressor function.     

Uranium uptake by some locally isolated and some reference bacterial species

In the present study, uranium absorption capacity of Bacillus pantothenticus and Bacillus megaterium, previously isolated from the environmental air surrounding the 60Co gamma source, is reported. Pseudomonas putida and Pseudomonas chlororaphis were used as reference species. Concerning uranium uptake, the local species were more efficient than the reference ones. The maximum uptake of uranium was achieved by B. megaterium and P. chlororaphis at 20 microg U mL(-1) and by B. pantothenticus at 30 microg U mL(-1). The transmission electron microscope examination indicated that uranium was absorbed onto the cell surface of the studied isolates. Furthermore, the increase in biomass concentration has shown an increase in the total amount of uranium removed. Dead cells exhibited uranium uptake to the same or greater extent than living cells. B. pantothenticus, P. putida, and P. chlororaphis achieved maximum uptake at pH 4.0, whereas for B. megaterium it was at pH 6.0. Temperature had an important role in uranium absorption of all the studied species except B. pantothenticus. Metabolic inhibitors did not affect the uptake.     

A branched fluorescent peptide probe for imaging of activated platelets

Novel fluorescent probes for thrombi and activated-platelet detection were developed that were based on the glycoprotein IIb/IIIa (GP-IIb/IIIa) binding sequence, Pro-Ser-Pro-Gly-Asp-Trp. Linear, Pro-Ser-Pro-Gly-Asp-Trp-Aha-Gly-Cys(Cy5.5)-NH(2) (1PF), and branched, (Pro-Ser-Pro-Gly-Asp-Trp-Aha)(2)-Lys-Gly-Cys(Cy5.5)-NH(2) (2PF), fluorescent-labeled peptide probes were synthesized. A third probe, also branched, (Pro-Ser-Pro-Gly-Glu-Trp-Aha)(2)-Lys-Gly-Cys(Cy5.5)-NH(2) (2CF), was synthesized as control. The platelet-binding activity of the probes was tested in clots generated from human platelet-rich plasma. Fluorescence reflectance imaging results showed that 2PF has a 16-fold increase in fluorescence intensity compared to the autofluorescence of clots. The linear conjugate, 1PF, and free dye did not show appreciable fluorescence enhancement. 2PF fluorescence was also found 5.5-fold higher than that of the control probe, 2CF. Overall, our results suggest that 2PF binds tightly to GP-IIb/IIIa and potentially can be used for in vivo imaging of thrombosis.     

Posttherapy pathologic stage predicts survival in patients with esophageal carcinoma receiving preoperative chemoradiation

BACKGROUND: In patients with locoregional carcinoma of the esophagus or esophagogastric junction who underwent preoperative chemoradiation, it is unclear whether survival was better predicted by pretherapy clinical stage or by posttherapy pathologic stage. METHODS: The authors studied 235 consecutive patients with pretherapy clinical Stage II, III, or IVA (according to American Joint Committee on Cancer criteria) carcinoma of the esophagus or esophagogastric junction who were treated with chemoradiation followed by esophagectomy. Posttherapy cancer status was classified using pathologic stage and semiquantitative assessment of residual carcinoma. Clinicopathologic features, residual carcinoma status, and pretherapy and posttherapy stage were compared with disease-free and overall survival. RESULTS: Posttherapy pathologic stage was Stage 0 in 29% of patients, Stage I in 11% of patients, Stage II in 34% of patients, Stage III in 20% of patients, and Stage IV in 6% of patients. Cancer downstaging occurred in 56% of patients. In univariate analysis, disease-free and overall survival were predicted by posttherapy pathologic stage (both with P < 0.001), margin status (P = 0.002 and P = 0.01, respectively), extent of residual carcinoma (both with P < 0.001), and downstaging (both with P = 0.001), but not by age, gender, type of cancer, pretherapy clinical stage, or preoperative regimen. However, in multivariate analysis, disease-free and overall survival were independently predicted by posttherapy pathologic stage (both with P = 0.02). Extent of residual carcinoma was a marginally significant predictor of overall survival (P = 0.04). CONCLUSIONS: Posttherapy pathologic stage was the best available predictor of outcome for patients with locoregional carcinoma of the esophagus or esophagogastric junction who underwent chemoradiation therapy followed by esophagectomy. The findings in the current study supported the concept of downstaging by preoperative therapy.