Yutaka Ogata

Repeat pulmonary resection for isolated recurrent lung metastases yields results comparable to those after first pulmonary resection in colorectal cancer.

Pulmonary resection for colorectal metastases is well accepted. However, the main cause of death after pulmonary resection is recurrence in the lung. The aim of this study was to clarify whether a repeat pulmonary resection was warranted in patients with recurrent lung metastases. The records of 76 patients undergoing initial pulmonary resection, including 14 patients undergoing a repeat operation for lung metastases, were reviewed for survival, operative morbidity, and mortality. Overall, pulmonary resection was performed 96 times in this group of patients. The operative mortality was 0%, morbidity involved only one case of major postoperative hemorrhage associated with the first operation. The cumulative 5-year survival rate for the 76 patients was 32%. After the second pulmonary operation, recurrence was identified in 79% (11 of 14) of the patients. In 10 patients with isolated lung recurrence after a first pulmonary resection, who showed no extrapulmonary disease before or at the time of first thoracotomy, the 3-year, and 5-year-survival rate after the second pulmonary resection was 67%, and 33%, respectively, comparing favorably with the survival rate in those who underwent primary pulmonary resection. In contrast, all 4 patients with extrapulmonary disease before or at the time of thoracotomy had poor prognosis. Repeat pulmonary operation for isolated recurrent colorectal metastases to the lung yielded results comparable to those after the first pulmonary resection in terms of operative mortality and survival in the absence of hilar/mediastinal lymph node or extrathoracic involvement.

Oncologic and functional results of total mesorectal excision and autonomic nerve-preserving operation for advanced lower rectal cancer.

PURPOSE:Total mesorectal excision contains two different procedures: autonomic nerve preservation, and autonomic nerve sacrifice. It is unclear whether autonomic nerve preservation is suitable curative procedure. We clarify the significance of autonomic nerve preservation for an advanced lower rectal cancer.METHODS:All 403 patients curatively resected between 1975 and 1999 were clinicopathologically studied. Between 1975 and 1984, all patients routinely received total mesorectal excision without autonomic nerve preservation (TME-P(−) group). Since 1985, total mesorectal excision with autonomic nerve preservation has been performed in 81 percent of patients (TME-P(+) group). The remaining patients received TME-P(−) because of suspicious invasion to autonomic nerve plexus. All clinical and pathologic data were entered into a computer database. Long-term follow-up was used to analyze the oncologic and functional results of TME-P(+) group compared with TME-P(−) group.RESULTS:The follow-up rate was 98.1 percent. In either Dukes A+B or Dukes C disease, the TME-P(+) group did not increase local recurrence or decrease ten-year disease-free survival compared with the TME-P(−) group of Period 1975 to 1984. The TME-P(−) group of Period 1985 to 1999 had the highest distant metastasis and the lowest survival rates than any other groups. Urinary or sexual function was well preserved in the TME-P(+) group. CONCLUSIONS:Autonomic nerve preservation is oncologically and functionally excellent and suitable for almost all patients with advanced lower rectal cancer. Intensive chemotherapy is needed for patients whose autonomic nerves were killed in suspicion of nerve invasion.

Expression of vascular endothelial growth factor and its receptor KDR (kinase domain-containing receptor)/Flk-1 (fetal liver kinase-1) as prognostic factors in human colorectal cancer.

AbstractBackground. To clarify the clinical significance of the expression of vascular endothelial growth factor (VEGF) and its receptor, kinase domain-containing receptor (KDR) in colorectal cancer, we evaluated the relationship between the expression of VEGF and KDR, and the microvessel counts and clinicopathological factors in colorectal cancer. Methods. A total of 259 specimens from sequential colorectal cancer patients who had undergone surgery were examined by the avidin-biotin peroxidase complex method, using anti-human VEGF, anti-human KDR, and anti-human von Willebrand factor antibodies. Results. The incidence of VEGF expression in the tumor cells of the patients with liver metastasis was significantly higher than that in the tumor cells of the patients without liver metastasis (67% vs 44%). The microvessel count at the tumor invasive edge in the patients whose tumor cells were positive for VEGF was significantly higher than that in the patients whose tumor cells were negative for VEGF (33.0 ± 7.8 vs 28.0 ± 7.9); the significant difference in microvessel counts was greater when there was a combination of VEGF and KDR expression. The overall survival rate of patients positive for VEGF was significantly (P = 0.0276) lower than that of those who were negative for VEGF. Although there was no significant difference (P = 0.0743) in the survival rates after potentially curative resection according to VEGF expression, the survival rate of the patients positive for both VEGF in tumor cells and KDR in endothelial cells was significantly (P = 0.0026) lower than that in the patients who were negative for VEGF and/or KDR. In addition, multivariate analysis revealed that the expression of both VEGF and KDR was an independent prognostic factor even after potentially curative resection. Conclusion. VEGF may be implicated in the definition of the malignant phenotype of colorectal cancer via tumor angiogenesis. VEGF and its receptor KDR expression in tumorous tissues could be useful prognostic factors in colorectal cancer.

A new ultimate anus-preserving operation for extremely low rectal cancer and for anal canal cancer

Abstract.To avoid permanent colostomy, we perform a new ultimate anus preserving operation for extremely low rectal cancer or for anal canal cancer. According to our pathologic study, two different removal methods of anal canal were theoretically considered. One is internal sphincter resection (ISR method), and the other is both deep-superficial external sphincter and internal sphincter resection (ESR method). Six patients received ISR and ten patients ESR. No severe intraoperative complications occurred and the postoperative course was uneventful. All patients receiving ISR had excellent anal function without soiling. Some patients receiving ESR sometimes complained of night soiling but satisfied the anus preservation. The median follow-up was 15 months, (range, 3–28 months). We had recurrences in two female patients receiving ISR. One had para-aortic and lateral lymph node recurrences without anastomotic recurrence. She underwent lateral and para-aortic lymphadenectomy, but died of lung metastasis, regardless of intensive chemotherapy. Another had pelvic recurrence with abdominal dissemination. She underwent abdominoperineal resection and is alive with pelvic re-recurrence. ISR and ESR are excellent procedures for anus preservation, but ISR needs a strict indication.

Expression of vascular endothelial growth factor as a prognostic factor in node-positive squamous cell carcinoma in the thoracic esophagus: Long-term follow-up study

To clarify the clinical significance of the expression of vascular endothelial growth factor (VEGF) in squamous cell carcinoma in the thoracic esophagus, particularly as a prognostic factor, we have investigated the correlation between VEGF expression in tumor cells and microvessel density (MVD), pathologic factors, and survival. A total of 92 specimens, each from a thoracic esophageal squamous cell cancer patient who underwent transthoracic curative R0 esophagectomy between 1991 and 1994, were examined immunohistochemically using anti-human VEGF and anti-human von Willebrand factor antibodies. The incidence of VEGF expression in the tumor cells was relatively low, at 23.9% of all specimens. There was no significant correlation between VEGF expression and histopathologic factors. The MVD at the tumor margin in patients with VEGF-positive tumor cells was significantly greater than that in VEGF-negative cases (35.2 ± 8.9 vs. 22.7 ± 8.2). The survival rate for patients with VEGF expression was significantly lower than that of those without VEGF expression; the same situation was found in node-positive patients but not in node-negative patients. In addition, multivariate analysis revealed that VEGF expression was an independent prognostic factor in node-positive patients. VEGF may be implicated in the definition of the malignant phenotype of squamous cell esophageal cancer via tumor angiogenesis. Accordingly, VEGF expression in the tumor cells could be a useful prognostic factor for esophageal cancer, particularly in node-positive patients.

Expression of tumor rejection antigens in colorectal carcinomas

The authors recently reported that the SART2 and SART3 antigens encode tumor epitopes recognized by HLA‐A24‐restricted and tumor‐specific cytotoxic T lymphocytes (CTLs) established from esophageal carcinoma patients. The current study investigated these antigens to explore a potential molecule for specific immunotherapy for colorectal carcinoma patients.

Primary linitis plastica carcinoma of the colon and rectum

Background. Linitis plastica carcinoma (LPC) usually shows a scirrhous growth pattern with a severe stromal desmoplastic reaction. Another growth pattern showing lymphangiosis carcinomatosa rather than scirrhous growth pattern, however, was noted. This study was designed to clarify the clinical and pathologic characteristics of colorectal LPC.

Elevated preoperative serum carcinoembrionic antigen level may be an effective indicator for needing adjuvant chemotherapy after potentially curative resection of stage II colon cancer.

To determine the prognostic factors and to rationalize adjuvant therapy, the clinicopathologic data of patients with a stage II colon cancer were analyzed retrospectively.

Inhibition of Liver Metastasis from Orthotopically Implanted Colon Cancer in Nude Mice by Transfection of the TIMP-1 Gene into KM12SM Cells

Abstract To determine whether the tissue inhibitor of metalloproteinases 1 (TIMP-1) can modulate in vivo tumor growth and metastasis, we transfected TIMP-1 cDNA into KM12SM human colon carcinoma cells and determined the implanted tumor volume and incidence of liver metastasis in orthotopically implanted colon cancer in nude mice. We also treated the implanted tumors with repeated intraperitoneal injections of recombinant human TIMP-1 (rTIMP-1), and compared the inhibitory efficacy on liver metastasis with that achieved by the TIMP-1 transfectants. The TIMP-1 transfectants had a significantly greater inhibitory effect, in association with TIMP-1 expression, on the growth of the primary tumor and on liver metastasis as compared with the controls. However, the intraperitoneal administration of rTIMP-1 did not decrease the rate of liver metastasis. In situ hybridization demonstrated that TIMP-1 mRNA in the cecal tumors implanted with the highly produced KM12SMT-2 cells with TIMP-1 was mainly expressed by the tumor cells. These results suggest that the increased expression of TIMP-1 in KM12SM cells was responsible for their decreased metastatic potential, and that the endogenous increase in TIMP-1 production by the tumor cells might be more effective for counteracting the matrix metalloproteinases (MMPs) in tumor tissue and for inhibiting liver metastasis from colon cancer than the exogenous administration of TIMPs.

Characteristic Morphology of Invasive Micropapillary Carcinoma of the Breast: An Immunohistochemical Analysis

OBJECTIVE Invasive micropapillary carcinoma of the breast is a distinct variant of breast cancer. In the present study, we analyzed potential immunophenotypic changes in invasive micropapillary carcinoma. METHODS Specimens from 15 patients with invasive micropapillary carcinoma were analyzed using clinicopathological and immunohistochemical methods. We also examined the relationship between clinicopathological factors using the Ki-67 labeling index. RESULTS Immunohistochemical staining for cytoplasmic p63 expression was seen in four (27%) tumors, and p63 nuclear expression was also observed in four (27%) tumors. Involucrin and 34betaE12 were expressed in the invasive micropapillary carcinoma component of nine (60%) and four (27%) tumors, respectively. Cytokeratin 5/6 was expressed in three (20%) tumors and cytokeratin 14 staining was negative in all tumors. In one tumor (case 3), vimentin, epithelial membrane antigen and cytokeratin 8/18 were co-expressed. Four tumors (27%) were negative for the estrogen receptor/progesterone receptor/HER2. However, 11 out of 15 (73%) tumors were positive for the estrogen receptor. The Ki-67 labeling index was significantly higher in cases with p63 tumor expression than in those without (P < 0.0001), and also higher in cases with lymph node metastasis than in cases without (P = 0.0029). CONCLUSIONS Nuclear expression of p63, involucrin and 34betaE12 were detected indicating squamous differentiation. Cytoplasmic p63 expression was also identified. The fact that the Ki-67 labeling index was significantly higher in such cases may have been associated with the aggressive behavior of these tumors. Our findings suggest that the characteristic morphology of invasive micropapillary carcinomas may be due to immunophenotypical and oncogenic changes.