[Perioperative management of two patients with renal malignant tumor involving the vena cava].

Two patients underwent resection of renal malignant tumors involving vena cava. Such tumors occasionally extend to the inferior vena cava with tumor thrombus and invasion to the lymph nodes and adjacent organs. Perioperative management of patients with these tumors is difficult because of the risk of pulmonary embolism and massive bleeding, and requires appropriate cooperation among the surgical team. In case 1, a 56-year-old man, renal cell carcinoma with tumor thrombus had extended into the intrahepatic vena cava. It was resected after isolating the liver from vena cava and incising the cross-clamped inferior vena cava without extracorporeal circulation or blood transfusion. A prosthetic graft replaced the inferior vena cava. In case 2, a 64-year-old woman, renal pelvis cancer adhered to the inferior vena cava and the mesentery with enlarged lymph nodes. It was separated from the inferior vena cava and removed with the ascending colon. The patient received a blood transfusion of approximately 2,000ml. Cardiomyopathy associated with a left ventricular outflow tract pressure gradient of 100mmHg required perioperative management. After surgery, both patients underwent controlled ventilation in the intensive care unit. After recovery, they were discharged without complications. We discuss perioperative management, with regard to the level of the tumor extension and perioperative complications.

Obstructive Colitis with Minor Perforation Induced by Double Sigmoid Adenocarcinoma.

A 72-year-old women was referred to our hospital because of lower left abdominal pain. Computed tomography showed prominent sigmoid colon dilation and double tumors on both the oral and anal sides. Surgical resection revealed an expanded sigmoid colon involved in double cancer that showed strong adhesion to the surrounding tissues. The pathological findings revealed obstructive colitis and minor perforation in the dilated colon. The minor perforation was considered to have been caused by fecal impaction in the closed cavity between the two tumors, resulting in an increase in colon pressure.

Prospective antitumor effects of the combination of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and cisplatin against esophageal squamous cell carcinoma.

PURPOSE: Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF family, which binds to death receptor (DR) 4 and DR5 to mediate apoptosis. Previously, we showed that the combination of TRAIL and cisplatin was effective against esophageal squamous cell carcinoma (ESCC) cell lines in vitro and in vivo, using one of the ESCC cell lines (KYSE 170). KYSE 110 is another ESCC cell line, but it lacks expression of decoy receptors. Thus, by using KYSE 110, we can eliminate any effects from two decoy receptors. METHODS: We used reverse transcription-polymerase chain reaction (RT-PCR) to reveal the expression of TRAIL receptors. Crystal violet staining and flow cytometry were done to confirm cytotoxicity and induction of apoptosis. KYSE 110 xenografted in nude mice was treated with TRAIL and cisplatin. The tumors were subsequently removed for microscopic studies. RESULTS: ESCC sensitive to the combination treatment in vitro was also sensitive to the treatment in vivo. Furthermore, induction of apoptosis resulted via the caspase cascade and the mitochondrial pathway. Low doses of both cisplatin and TRAIL sufficed to obtain these effects. CONCLUSION: These findings imply that in clinical application, low doses of both agents could be administered to minimize side effects, while augmenting tumoricidal activities.

Cisplatin-dependent upregulation of death receptors 4 and 5 augments induction of apoptosis by TNF-related apoptosis-inducing ligand against esophageal squamous cell carcinoma.

TNF-related apoptosis-inducing ligand (TRAIL) is a member of the TNF superfamily known to induce apoptosis in a variety of cancers. The purpose of our study was to examine the effects of TRAIL in combination with cisplatin against esophageal squamous cell carcinoma (ESCC) cell lines in vitro and in vivo, and to elucidate underlying molecular mechanisms. Expression profiles of TRAIL receptors were investigated in 19 ESCC (KYSE) cell lines using RT-PCR. Crystal violet staining assays were performed to reveal the sensitivity against TRAIL. Flow cytometric analyses of apoptosis induction and TRAIL receptor expression were performed. Furthermore, Western blot was used to clarify the apoptosis pathway involved, and a nude-mouse xenograft model was used to show effects in vivo. Results show that death receptors (DR) 4 and 5 were expressed in 100% of the cell lines, and 79% (15/19) expressed 4 TRAIL receptors. There was only 1 cell line without decoy receptor expression. Eighteen cell lines were resistant to TRAIL, but in some, the combination treatment with cisplatin could overcome this resistance. They underwent apoptosis via activation of caspase-8 and -3, and cisplatin-dependent upregulation of DR4 and 5 was detected. Furthermore, pretreatment with cisplatin followed by TRAIL resulted in significant tumoricidal effects. Finally, systemic administration of TRAIL with cisplatin synergistically suppressed tumor growth of ESCC xenografts in nude mice. These results provide a significance of cisplatin-induced upregulation of death receptors as apoptosis-inducing machinery, and it was suggested that sequential administration of cisplatin and TRAIL might be a feasible chemotherapeutic regimen against ESCC.

A new specific gene expression in squamous cell carcinoma of the esophagus detected using representational difference analysis and cDNA microarray.

OBJECTIVES: To detect new specific gene expressions in squamous cell carcinoma of the esophagus. METHODS: Representational difference analysis of cDNA (cDNA RDA) was applied to a human esophageal cancer cell line (KYSE170) and a human esophageal epithelial cell line (HEEC-1). RESULTS: LAGE-1 was expressed specifically in KYSE170, but not in HEEC-1. It is also expressed in 27% of esophageal cancer cell lines (3/11) and 33% of esophageal cancer tissues (10/30), but not in other HEECs, normal esophageal epithelium, or other normal tissues except testis, ovary and kidney. The expression of LAGE-1 is strongly correlated with that of MAGE-A1 (p = 0.013, Fisher's exact probability test). Fibronectin, cytokeratin 6B, cytokeratin 19, cyclin D2 and Ten-m2 were detected as candidates for downregulated genes. Reduced expression profiles of them were also identified using cDNA microarrays. The expression of LAGE-1 was induced by 5'-aza-2'-deoxycytidine (5Aza-dC) and trichostatin A (TSA) in esophageal cancer cell lines, which did not express LAGE-1. In HEECs, 5Aza-dC induced LAGE-1 expression, but TSA did not. CONCLUSIONS: LAGE-1 expression was detected in esophageal cancer by cDNA RDA. LAGE-1 might have the potential to be a target antigen for anti-tumoral immunotherapy in esophageal cancers because of its tumor-specific expression similar to that of MAGE-A1.

Prognostic significance of dysadherin expression in esophageal squamous cell carcinoma.

OBJECTIVE: Dysadherin is a cancer-associated cell membrane glycoprotein that has been reported to downregulate E-cadherin expression and promote metastasis. To evaluate the role of dysadherin in metastasis of esophageal squamous cell carcinoma (ESCC), we examined dysadherin and E-cadherin expression in patients with this cancer. METHODS: Dysadherin and E-cadherin expression was evaluated in 117 ESCC patients (pT1, 31; pT2, 30; pT3, 39; pT4, 17) by immunohistochemistry. The findings were compared with the clinicopathological data of the patients. RESULTS: Both dysadherin and E-cadherin were localized to the cell membrane. Thirty patients (29.1%) had tumors positive for dysadherin and 41 patients (35.0%) had tumors positive for E-cadherin. Tumors showing dysadherin positivity and negative E-cadherin expression had a significantly worse prognosis than other tumors. When the patients with dysadherin- positive tumors were combined with E-cadherin-negative patients, this group had a worse prognosis (p < 0.0001). Cox multivariate analysis revealed that dysadherin expression was an independent prognostic factor for ESCC (p = 0.003), but E-cadherin expression was not. CONCLUSION: Combined analysis of dysadherin and E-cadherin expression may help to predict the prognosis of patients with ESCC. Our results suggested that expression of dysadherin by this cancer may partly explain the poor prognosis of patients with preservation of E-cadherin expression.