Investigating the Follow-up Period after ALTA Sclerotherapy Using Transanal Ultrasonography.

Objectives: This study aims to clarify the appropriate follow-up period after aluminum potassium sulfate and tannic acid (ALTA) sclerotherapy for internal hemorrhoids by transanal ultrasonography. Methods: Forty-four patients (98 lesions) who underwent ALTA sclerotherapy were analyzed. Transanal ultrasonography was performed pre and post-ALTA sclerotherapy to observe the thickness and the internal echo image of hemorrhoid tissue. Patients who developed complications were excluded. Results: No recurrence in 12 months was observed in 44 patients. After 1-3 months of ALTA sclerotherapy, hemorrhoids were observed in the low-echo imaging region. During this period, hemorrhoidal tissue was observed thickest by granulation. Moreover, hemorrhoid tissue contracted by fibrosis formed 5-7 months post-ALTA sclerotherapy, with a thinner hemorrhoid. Furthermore, hemorrhoids hardened and regressed with intense fibrosis 12-months after the therapy and eventually became thinner than pre-ALTA sclerotherapy. Conclusions: After ALTA sclerotherapy, the suggested follow-up period with and without the development of complications is ～6 and ～3 months, respectively.

[Urine Protein/Creatinine Ratio Measurement Is Useful to Continue Anti-Angiogenic Agent Treatment].

BACKGROUND: Aside effect of anti-angiogenic agent treatment is proteinuria. Evaluation of the severity of adverse effects and the decision to discontinue treatment is based on the qualitative analysis of urinary proteins. However, a qualitative analysis result may not be indicative of the actual amounts of protein excreted. In this study, we evaluated the possibility of using the urine protein/creatinine ratio(UPCR), instead of a qualitative urine analysis, to monitor patients treated with antiangiogenic agents. METHODS: Urinalysis data of patients receiving anti-angiogenic agents-bevacizumab, ramucirumab, or aflibercept-were retrospectively analyzed from clinical records. Acorrelation between the urine protein content(qualitative and quantitative analyses)and continuity of anti-angiogenic agent treatment was evaluated. RESULTS: Atotal of 24 patients (age, 70.83±7.45 years)who received treatment for colorectal cancer(n=17), lung cancer(n=4), gastric cancer(n=2), and breast cancer(n=1)were included. One hundred and sixty-five urinalysis results were collected. Alinear correlation between the qualitative urinalysis results(1+to 3+)and UPCR(r=0.746, p<0.01)was obtained. In patients with a urine protein content of 2+(qualitative analysis), the UPCR was <2.0 for 25 patients and ≥2.0 but <3.5 for 4 patients. Similarly, in patients with a urine protein content of 3+, the UPCR was <2.0 for 3 patients and ≥2.0 but <3.5 for 1 patient. Seventeen patients with a urine protein content of 2+ and 3 patients with a urine protein content of 3+ discontinued treatment with anti-angiogenic agents before estimation of the UPCR could be performed. These figures were reduced to 4 patients and 2 patients, respectively, following UPCR assessment. CONCLUSIONS: Switching the estimation of proteinuria from a qualitative analysis to UPCR might lead to better safety monitoring and prevent unnecessary discontinuation of anti-angio- genic agent treatment.

Severe gastrointestinal hemorrhage related to everolimus: a case report.

Everolimus is an mTOR (the mammalian target of rapamycin) inhibitor, which is used for the treatment of advanced renal cell carcinoma. Life-threatening hemorrhages are extremely rare adverse effect of everolimus. We herein report a successfully treated case of severe everolimus-related gastrointestinal hemorrhage by emergency surgical resection for patient with advanced renal cell carcinoma. A 72-year-old male was diagnosed with renal cell carcinoma, for which everolimus was administered after unsuccessful treatment with sunitinib and sorafenib. The patient suddenly developed hematemesis 4 weeks after administration. Upper gastrointestinal endoscopy showed gastric antral vascular ectasia. Once the hemorrhage was successfully cauterized by argon plasma coagulation, everolimus was discontinued. However, the patient after re-administration of everolimus developed hematemesis again and exhibited hemorrhage shock. Since therapeutic endoscopy could not achieve hemostasis, the patient underwent emergency distal gastrectomy with Billroth I reconstruction. The patient's vital signs and hemoglobin level stabilized after the surgery. Thereafter, the patient made a satisfactory recovery, and was discharged on postoperative day 10.

Expression of CXCR-4 and IDO in human colorectal cancer: An immunohistochemical approach.

C-X-C chemokine receptor type 4 (CXCR4), the receptor for the chemokine stromal cell-derived factor (SDF)-1 [also known as C-X-C motif chemokine 12 (CXCL12)], is involved in lymphocyte trafficking. Recent studies have demonstrated that, during pregnancy, a placental enzyme called indoleamine 2, 3-dioxygenase (IDO) exerts a key role in suppressing the maternal T-cell response against the fetus. In the present study, the significance of CXCR4 and IDO expression in human colorectal cancer (CRC) has been investigated by immunohistochemical assay, and their association with survival was analyzed. Tumor specimens (n=60) from patients with different American Joint Committee on Cancer (AJCC) stages of CRC (I or IV) were assessed. In the stage IV group, 23 of 30 cases (77%) stained positive for CXCR4, and 9 of 30 (30%) were positive for IDO. By contrast, in the stage I group, 7 of 30 cases (23%) stained positive for CXCR4, and 15 of 30 cases (50%) were positive for IDO. The 5-year survival rate of those with high CXCR4 expression in tumor specimens (n=30) was significantly worse compared with those with negative CXCR4 expression (16.3 vs. 60.7%, P=0.02). By contrast, the 5-year survival rate of those with high IDO expression in tumor specimens (n=24) was not significantly different compared with those with negative IDO expression (36.4 vs. 56.8%). In the stage I group, 4 patients in the high IDO expression group (n=15) had distant metastases (2 in the liver 1 in the brain, and 1 in the lung). Taken together, CXCR4 appears to be a novel predictive indicator of survival, and IDO expression in the early stage may be a predictor of distant metastasis.

The Usefulness of Diffusion MRI in Detection of Lymph Node Metastases of Colorectal Cancer.

The aim of this study was to assess the sensitivity and specificity of preoperative diagnosis by diffusion magnetic resonance imaging (D-MRI) for lymph node metastasis of colorectal cancer. The b-value represents the diffusion factor (measured in s/mm(2)) and the strength of the diffusion gradients. The b-value used in this study was 1,000 s/mm(2). A total of 119 patients underwent D-MRI before resection of primary colorectal cancer (52 of the rectum, 67 of the colon) at our hospital between February 2005 and April 2006. Lymph node metastases judged by D-MRI were compared with postoperative pathological results. The form of lymph node metastasis was classified either as abundant or scarce type. The predictive values for lymph-node metastasis (sensitivity and specificity) by D-MRI were calculated from the result of this classification and lymph-node size. The study was divided into two periods: before the consensus meeting in January 2006, (n=79) (P-I), and after the adjustment of the criteria to improve the sensitivity and specificity based on the results of P-I (n=40) (P-II). Detection of lymph node metastasis using D-MRI in P-I had sensitivity of 61%, specificity of 73%, positive predictive value (PPV) of 55%, and negative predictive value (NPV) of 77%, while in P-II, these values improved to 79%, 95%, 94%, and 83%, respectively. Specificity and PPV for P-II were significantly higher than those for P-I (p<0.05). The diameter of lymph nodes judged to be metastatic on D-MRI (P-I vs. P-II: n=32 vs. 16) was 10.3±5.4 (3-28) vs. 9.1±3.0 (4-14) mm; 11.5±6.2 (4-28) vs. 9.2±3.1 (4-14) mm for truly positive nodes (n=18 vs. 15), and 6±3.8 (3-14) vs. 8 mm for false-positive nodes (n=14 vs. 1). On the other hand, lymph nodes judged negative by D-MRI (n=47 vs. 24) was 5.9±2.4 (3-16) vs. 5.7±2.8 (2-15) mm; 5.9±2.1 (3-16) vs. 5.3±2.1 (2-8) mm for truly negative (n=36 vs. 20), and 5.7±2.7 (3-12) vs. 7.8±4.9 (4-15) mm for false negative (n=11 vs. 4). As to the form of metastasis, all truly positive nodes were of the abundant type, and 6/11 (55%) in P-I and 1/4 (25%) in P-II false-negatives were of the scarce type. In conclusion, D-MRI seems useful for preoperative detection of metastatic lymph nodes in colorectal cancer, especially if the node is hyperintense and more than 9 mm in diameter.

Thymidine phosphorylase mRNA expression may be a predictor of response to post-operative adjuvant chemotherapy with S-1 in patients with stage III colorectal cancer.

The aim of the present study was to investigate markers in surgically resected specimens of colorectal cancer that can be used to predict the response to chemotherapy. The mRNA expression levels of enzymes involved in 5-fluorouracil (5-FU) metabolism and folate metabolism were measured in formalin-fixed, paraffin-embedded tumor sections obtained from the primary tumors of 54 patients with resected stage II or III colorectal cancer who received S-1 for one year. The 5-FU metabolizing enzymes studied were thymidylate synthase, dihydropyrimidine dehydrogenase and thymidine phosphorylase (TP). The folate metabolizing enzymes studied were folypolyglutamate synthetase, γ-glutamyl hydrolase and dihydrofolate reductase. The associations between the mRNA expression levels of these enzymes and clinical variables were investigated. Tumors were classified as exhibiting high or low expression as compared with the median mRNA expression level of each metabolizing enzyme defined as the cutoff value. The associations between the high and low expression levels of each enzyme and disease-free survival (DFS) were analyzed with the use of Kaplan-Meier curves and the log-rank test. DFS was not significantly associated with the relative mRNA expression level of any metabolizing enzyme in the study group as a whole, but there was a trend toward longer DFS in patients with high TP expression (P=0.066). In patients with stage III colorectal cancer, high TP expression was associated with significantly improved outcomes compared with low TP expression (P=0.039). These results indicate that the mRNA expression of TP, a metabolizing enzyme of 5-FU, is a significant predictor of response to post-operative chemotherapy with S-1 in patients with stage III colorectal cancer.

Feasibility study of S-1 adjuvant chemotherapy in patients with colorectal cancer.

BACKGROUND: We evaluated the safety, efficacy, and compliance of 1-year treatment with S-1 in patients with stage II/III resectable colorectal cancer. METHODS: S-1 was administered orally in two divided doses daily. The dose was assigned according to body surface area (BSA) as follows: BSA <1.25 m(2), 80 mg/day; BSA ≥1.25 to <1.5 m(2), 100 mg/day; and BSA ≥1.5 m(2), 120 mg/day. S-1 was given for 28 consecutive days, followed by a 14-day rest. The study objects were the rate of completion of treatment as planned at 1 year, the ratio of the actually administered dose to the planned dose at 1 year, and the total number of days of treatment. RESULTS: At 1 year, the rate of completion of treatment as planned was 77.7 % (42/54 patients), and the ratio of the actually administered dose to the planned dose was 82.9 %. The mean and median total numbers of days of treatment were 209 and 252, respectively. Grade 3 or higher toxicity (watery eyes) occurred in only 1 patient. CONCLUSION: S-1 adjuvant chemotherapy had acceptable compliance, safety, and efficacy in patients with colorectal cancer. S-1 adjuvant chemotherapy is considered a possible standard treatment regimen for colorectal cancer.

Increased lymphatic vessels in patients with encapsulating peritoneal sclerosis.

BACKGROUND: The angiogenic response is partly involved in the progression of encapsulating peritoneal sclerosis (EPS). However, the details of the angiogenic response, especially for lymphatic vessels in patients with EPS, remain unclear. In addition, because of technical limitations, morphology studies reported to date have examined only the parietal peritoneum. The morphologies of parietal and visceral lymphatic vessels in patients with EPS both need to be analyzed. METHODS: We examined peritoneal samples from 18 patients with EPS who underwent enterolysis of the visceral peritoneum and compared them with samples from 17 autopsy cases (controls). To examine the angiogenic response, we performed immunohistochemistry for the endothelial markers CD34 (blood vessels) and podoplanin (lymphatic vessels) and for the cell proliferation marker Ki-67. Immunogold electron microscopy analysis for podoplanin was also performed. In 7 of 18 cases, we compared differences in the angiogenic response of the parietal and visceral peritoneal membranes. RESULTS: Angiogenic responses were more frequent in the compact zone than in regenerated layers. The number of capillaries positive for anti-CD34 and anti-podoplanin monoclonal antibodies per unit area of visceral peritoneal tissue was, respectively, 41.1 ± 29.3/mm(2) in EPS patients and 2.7 ± 4.4/mm(2) in controls (p ≤ 0.01) and 48.1 ± 43.9/mm(2) in EPS patients and 4.1 ± 5.4/mm(2) in controls (p ≤ 0.01). The percentage of capillaries positive for anti-Ki-67, CD34, and podoplanin was 4.6% in EPS patients (p ≤ 0.01) and 0.8% in controls (p = 0.09). The immunogold electron microscopy analysis revealed that podoplanin was localized to endothelial cells with anchoring filaments, a specific feature of lymphatic vessels. Furthermore, compared with parietal peritoneal membrane, visceral peritoneal membrane had a more prominent podoplanin-positive capillary profile, but not a prominent CD34-positive capillary profile. In addition, fibroblast-like cells double-positive for podoplanin and smooth muscle actin were markedly increased in the degenerated layer, as previously reported. CONCLUSIONS: Our study demonstrated that lymphatic vessels are increased in the visceral peritoneum of patients with EPS.

Serum vitamin D levels and survival of patients with colorectal cancer: post-hoc analysis of a prospective cohort study.

BACKGROUND: Recently, serum 25-hydroxyvitamin D (25OHD) levels were shown to be associated with the survival of patients with colorectal cancer. However, 25OHD levels were measured a median of 6 years before diagnosis or were predicted levels. In this study, we directly measured serum 25OHD levels at surgery and examined the association with survival among patients with colorectal cancer. METHODS: We started a prospective cohort study to find prognostic factors in patients with colorectal cancer from 2003 to 2008 and stored serum samples and clinical data. As part of a post-hoc analysis, serum 25OHD levels were measured by radioimmunoassay. Association between overall survival and serum 25OHD levels were computed using the Cox proportional hazard model adjusted for month of serum sampling as well as age at diagnosis, gender, cancer stage, residual tumor after surgery, time period of surgery, location of tumor, adjuvant chemotherapy and number of lymph nodes with metastasis at surgery. Unadjusted and adjusted hazard ratios (HR) and 95% confidence intervals (95% CI) were determined. RESULTS: Serum 25OHD levels were measured in 257 patients. Only 3% had sufficient levels (30 ng/ml and greater). Based on month of blood sampling, an annual oscillation of 25OHD levels was seen, with levels being lower in spring and higher in late summer. Higher 25OHD levels were associated with better overall survival under multi-variate analysis (HR, 0.91: 95% CI, 0.84 to 0.99, P = 0.027). CONCLUSIONS: These results suggest that higher 25OHD levels at surgery may be associated with a better survival rate of patients with colorectal cancer.

Clinicopathological features of perforated colorectal cancer.

UNLABELLED: The aim of this retrospective study was to determine clinicopathological factors pertinent to the prognosis of perforated colorectal cancer (PCRC). PATIENTS AND METHODS: A retrospective review of clinical records of 17 cases of emergency primary resection for PCRC (stage IIIa in 2, stage IIIb in 6 and stage IV in 9) was performed. RESULT: The 5-year survival rate was 31% (31% for stage III and 12% for stage IV). When compared with non-PCRC (533 cases) in stage III (78.8%) or stage IV (14.8%), the 5-year survival rate of stage III perforated colorectal cancer was clearly worse (p<0.01) than the non-perforated counterpart. For stage IV, however, the two groups had a similar prognosis. MST of the PCRC was 31 months for stage III and 12 months for stage IV. Approximately half of the recurrence pattern of stage III (75%), or stage IV (44%) PCRC was peritoneal carcinomatosis. As for the type of operations performed, Hartmann's procedure was the preferred technique (71%), for which mortality and morbidity rate were both low. CONCLUSION: Because of the high incidence of peritoneal carcinomatosis and low 5-year survival rate, stage III PCRC should be regarded as a stage IV disease, for which postoperative chemotherapy seems essential.

Arterial infusion chemotherapy in patient with repeated recurrent tumor of cecal cancer: report of a case.

PURPOSE: We report a patient with a repeated recurrent tumor after Right-hemicolectomy for advanced cecal cancer who was treated by intra-arterial infusions of 5-fluorouracil (5-FU). METHODS: A computed tomography scan revealed a pelvic mass involving the psoas major muscle and quadratos lumborum muscle, in contact with the widely projecting toward L2-S2. The fluorodeoxyglucose-positron emission tomography (FDG-PET) revealed an accumulation spot in the same place. This case was deemed in operable, and one-shot bolus of 5-FU was administered through the tumor feeding arteries: the left 3rd, 4th lumbar, and ilio -- lumbar arteries at a dosage of 250 mg/body from each artery. RESULTS: A partial regression of the tumor was observed by computed tomography. The serum level of carbohydrate antigen 19-9 returned normal in 8 months. During chemotherapy, the side effect and complications were tolerable, and she experienced only grade-1 nausea caused by 5-fluorouracil. CONCLUSION: A long-time, intra-arterial 5-fluorouracil infusion could control effectively and safely.

Poorly differentiated adenocarcinoma of the colon and rectum: clinical characteristics.

BACKGROUND/AIMS: The aims of this study were to assess the prognosis and histopathological factors of poorly differentiated colorectal adenocarcinoma, and the clinical relevance of the proposed histopathological sub classifications. METHODOLOGY: Fifty eight patients with poorly differentiated adenocarcinoma were enrolled in this study. According to the lymphatic canal spread in tumor tissue, they were classified into lymphangitic type (tumor spread beyond the intra mucosal tumor space through the lymphatic canal widely) and non-lymphangitic type (tumor spread within that space). Next, they were sub classified into medullary, intermediate and scirrhous types according to the amount of fibrous stroma. In addition, immunohistological examinations were performed on the expression of an intercellular adhesion molecule (E-cadherin). RESULTS: In 33 cases (57%) Lymphangitic type was present and in 25 cases non-lymphangitic type (43%) was present. In the lymphangitic types, 5 cases were medullary type (15%), 17 cases were intermediate type (52%) and 11 cases were scirrhous type (33%) that included 2 cases of signet ring cell carcinoma. In the non-lymphangitic types, medullary type was dominant (20 cases, 80%) while intermediate type and scirrhous type were 3 cases (12%) and 2 cases (8%), respectively. The survival rates were calculated for both types and a large difference was found in terms of 5-year survival rate; 0% for lymphangitic type and 72% for non-lymphangitic type (p<0.05). There was no correlation found between the expression of cadherin and the subclassification. CONCLUSIONS: In conclusion, a wide tumor infiltration and growth in lymphatic vessels appears to be an important prognostic factor for poorly differentiated adenocarcinoma compared to the metastasis patterns.

Synergistic induction of antigen-specific CTL by fusions of TLR-stimulated dendritic cells and heat-stressed tumor cells.

Dendritic cell (DC)/tumor cell fusion cells (FCs) can induce potent CTL responses. The therapeutic efficacy of a vaccine requires the improved immunogenicity of both DCs and tumor cells. The DCs stimulated with the TLR agonist penicillin-killed Streptococcus pyogenes (OK-432; OK-DCs) showed higher expression levels of MHC class I and II, CD80, CD86, CD83, IL-12, and heat shock proteins (HSPs) than did immature DCs. Moreover, heat-treated autologous tumor cells displayed a characteristic phenotype with increased expression of HSPs, carcinoembryonic Ag (CEA), MUC1, and MHC class I (HLA-A2 and/or A24). In this study, we have created four types of FC preparation by alternating fusion cell partners: 1) immature DCs fused with unheated tumor cells; 2) immature DCs fused with heat-treated tumor cells; 3) OK-DCs fused with unheated tumor cells; and 4) OK-DCs fused with heat-treated tumor cells. Although OK-DCs fused with unheated tumor cells efficiently enhanced CTL induction, OK-DCs fused with heat-treated tumor cells were most active, as demonstrated by: 1) up-regulation of multiple HSPs, MHC class I and II, CEA, CD80, CD86, CD83, and IL-12; 2) activation of CD4+ and CD8+ T cells able to produce IFN- gamma at higher levels; 3) efficient induction of CTL activity specific for CEA or MUC1 or both against autologous tumor; and 4) superior abilities to induce CD107+ IFN-gamma+ CD8+ T cells and CD154+ IFN-gamma+ CD4+ T cells. These results strongly suggest that synergism between OK-DCs and heat-treated tumor cells enhances the immunogenicity of FCs and provides a promising means of inducing therapeutic antitumor immunity.

Streptococcal preparation OK-432 promotes fusion efficiency and enhances induction of antigen-specific CTL by fusions of dendritic cells and colorectal cancer cells.

Dendritic/tumor fusion cell (FC) vaccine is an effective approach for various types of cancer but has not yet been standardized. Antitumor activity can be modulated by different mechanisms such as dendritic cell (DC) maturation state. This study addressed optimal strategies for FC preparations to enhance Ag-specific CTL activity. We have created three types of FC preparations by alternating fusion cell partners: 1) immature DCs fused with autologous colorectal carcinoma cells (Imm-FCs); 2) Imm-FCs followed by stimulation with penicillin-inactivated Streptococcus pyogenes (OK-432) (Imm-FCs/OK); and 3) OK-432-stimulated DCs directly fused to autologous colorectal carcinoma cells (OK-FCs). Both OK-FCs and Imm-FCs/OK coexpressed the CEA, MUC1, and significantly higher levels of CD86, CD83, and IL-12 than those obtained with Imm-FCs. Short-term culture of fusion cell preparations promoted the fusion efficiency. Interestingly, OK-FCs were more efficient in stimulating CD4(+) and CD8(+) T cells capable of high levels of IFN-gamma production and cytolysis of autologous tumor or semiallogeneic targets. Moreover, OK-FCs are more effective inducer of CTL activation compared with Imm-FCs/OK on a per fusion cell basis. The pentameric assay confirmed that CEA- and MUC1-specific CTL was induced simultaneously by OK-FCs at high frequency. Furthermore, the cryopreserved OK-FCs retained stimulatory capacity for inducing antitumor immunity. These results suggest that OK-432 promotes fusion efficiency and induction of Ag-specific CTL by fusion cells. We conclude that DCs fused after stimulation by OK-432 may have the potential applicability to the field of antitumor immunotherapy and may provide a platform for adoptive immunotherapy in the clinical setting.

[Multiple hepatic metastases of colon cancer responding to combined therapy with TS-1 and CPT-11--a case report].

We treated a patient with multiple liver metastases arising from colon cancer in whom the metastatic tumors were responsive to treatment with the combination of TS-1 and CPT-11. The patient was a 71-year-old woman with cancer of the ascending colon and metastatic hepatic tumors. She had undergone surgery on July 28, 2004, and abdominal contrast CT scans obtained after discharge from hospital revealed numerous LDA (low-density areas) in both lobes of the liver. The patient was given ambulatory chemotherapy with TS-1 (120 mg/day on days 1-14) and CPT-11 (100 mg/day on days 1 and 8). After completion of 2 courses of chemotherapy, abdominal contrast CT scans revealed that most of the LDAs in both lobes of the liver had disappeared, and the patient was judged to have achieved PR. No adverse reactions were observed except for a slight decrease of WBC, and her chemotherapy is being continued at present. This case suggests that the combination of TS-1 and CPT-11 may be an effective form of chemotherapy for the treatment of colon cancer with multiple hepatic metastases.

Dendritic cells fused with allogeneic colorectal cancer cell line present multiple colorectal cancer-specific antigens and induce antitumor immunity against autologous tumor cells.

The aim of antitumor immunotherapy is to induce CTL responses against autologous tumors. Previous work has shown that fusion of human dendritic cells and autologous tumor cells induce CTL responses against autologous tumor cells in vitro. However, in the clinical setting of patients with colorectal carcinoma, a major difficulty is the preparation of sufficient amounts of autologous tumor cells. In the present study, autologous dendritic cells from patients with colorectal carcinoma were fused to allogeneic colorectal tumor cell line, COLM-6 (HLA-A2(-)/HLA-24(-)), carcinoembryonic antigen (CEA)(+), and MUC1(+) as an alternative strategy to deliver shared colorectal carcinoma antigens to dendritic cells. Stimulation of autologous T cells by the fusion cells generated with autologous dendritic cells (HLA-A2(+) and/or HLA-A24(+)) and allogeneic COLM-6 resulted in MHC class I- and MHC class II-restricted proliferation of CD4(+) and CD8(+) T cells, high levels of IFN-gamma production in both CD4(+) and CD8(+) T cells, and the simultaneous induction of CEA- and MUC1-specific CTL responses restricted by HLA-A2 and/or HLA-A24. Finally, CTL induced by dendritic cell/allogeneic COLM-6 fusion cells were able to kill autologous colorectal carcinoma by HLA-A2- and/or HLA-A24-restricted mechanisms. The demonstration of CTL activity against shared tumor-associated antigens using an allogeneic tumor cell line, COLM-6, provides that the presence of alloantigens does not prevent the development of CTL with activity against autologous colorectal carcinoma cells. The fusion of allogeneic colorectal carcinoma cell line and autologous dendritic cells could have potential applicability to the field of antitumor immunotherapy through the cross-priming against shared tumor antigens and provides a platform for adoptive immunotherapy.

Gasless laparoscopic surgery using a new intra-abdominal fan retractor system: an experience of 500 cases.

AIM: The aim of this study is to report the feasibility of a newly developed intra-abdominal fan retractor system for use in gynecologic laparoscopic surgery. METHODS: Five hundred women undergoing gasless laparoscopic surgery using the abdominal wall lifting device were included in the study. The intraoperative and postoperative courses, and complications were examined. RESULTS: The intra-abdominal retractor system provided adequate exposure in all cases, except for one patient with morbid obesity. Neither the presence of the intra-abdominal retractor blades nor the mechanical arm interfered with the placement of instruments during surgery. No complications related to the use of gasless laparoscopy were encountered in this study period. CONCLUSION: The new intra-abdominal fan retractor system is feasible in gynecologic laparoscopic surgery.

The activities of thymidine phosphorylase and dihydropyrimidine dehydrogenase in colorectal cancer depend on where the sample is taken.

The significance of tumor tissue thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) levels, as well as the TP/DPD ratio have recently been reported as prognostic factors and for custom-made chemotherapy. However, there have been no distinct studies on actual tumor sampling methods. For 16 patients who had undergone resection of advanced colorectal cancer, we: i) measured TP and DPD levels in different portions of the tumor using enzyme-linked immunosorbent assay (ELISA); ii) categorized the tumor into an edge, center, and base area, and histo-pathologically calculated the ratio of cancer cell/cancer cell + stromal cell; and iii) examined the correlation between cancer and stromal cell TP expression and TP value. Variation within the same tumor was seen in each activity level and TP/DPD ratio. The ratio of cancer cell in the edge area was high, with the ratio of stromal cell in the center and base areas increasing in that order. A correlation was seen between TP expression and TP levels, and TP expression was evident in the stromal cells. It is therefore recommended to sample the edge area for tumor TP levels.

Expression of matrix metalloproteinase 7, laminin and type IV collagen-associated liver metastasis in human colorectal cancer: immunohistochemical approach.

BACKGROUND/AIMS: Matrix metalloproteinase 7 (MMP-7) plays an important role in vessel invasion and metastasis in human colorectal cancer. METHODOLOGY: The significance of MMP-7, laminin and type IV collagen expression in human colorectal cancer was investigated by immunohistochemical assay, and the correlation with liver metastasis was analyzed. RESULTS: In a synchronous metastasis group, 26 of 36 cases (72%) showed positive staining of MMP-7: There were 32 cases (89%) in the lymph channel and 28/32 cases (87%) in the vessels, and 17/34 cases (50%) showed a positive rate of laminin. In the metachronous metastasis group, 14 of 30 cases (47%) showed positive staining of MMP-7: There were 19 cases (63%) in the lymph channel and 13/19 cases (69%) in the vessels, and 17/30 cases (57%) showed a positive rate of laminin. In the control group, which was a 5-year disease-free group, despite there being no significant clinicopathological factors compared with the other two groups, 17 of 37 cases (51%) showed positive staining of MMP-7: There were 12 cases (37%) in the lymph channel and 6 cases (18%) in the vessels, and 2/31 cases (5%) showed a positive rate of laminin. The expression of type IV collagen attenuated in 19 out of 32 cases (59%) in Group S, 10 out of 19 cases (53%) in Group M, and 14 out of 37 cases (38%) in Group C, with no significant differences among the groups. Thus, the metastatic groups were significantly higher than the control group in terms of expression of laminin and MMP-7 in the lymph channel. CONCLUSIONS: These findings suggest that laminin and the expression of MMP-7 in the lymph channel is a useful parameter for predicting liver metastasis.

Induction of antigen-specific CD4- and CD8-mediated T-cell responses by fusions of autologous dendritic cells and metastatic colorectal cancer cells.

Human metastatic colorectal carcinomas (CRCAs) express carcinoembryonic antigen (CEA) and/or MUC1 tumor-associated antigens as potential targets for the induction of active specific immunity. In the present study, freshly isolated metastatic CRCA cells were successfully fused with immature autologous human monocyte-derived dendritic cells (DCs). The created heterokaryons (DC/CRCA) coexpress the CRCA-derived CEA and MUC1 antigens and DC-derived MHC class II and costimulatory molecules. The fusion cells were functional in stimulating the proliferation of autologous T cells. In addition, both CD4(+) and CD8(+) T cells were activated by fusion cells, as demonstrated by the production of high levels of IFN-gamma. More importantly, coculture of fusion cells with patient-derived peripheral blood mononuclear cells (PBMCs) resulted in the induction of antigen-specific cytotoxic T lymphocytes (CTLs). CTLs were effective at lysis of not only autologous CRCA cells but also the CEA and/or MUC1-positive and HLA partially matched target cells. Antigen-specific CTL responses were confirmed by tetrameric analysis. Coculture of PBMCs with fusion cells resulted in increased frequency of CEA- and MUC1-specific CTLs simultaneously. Taken together, these results indicate that freshly isolated human metastatic CRCA cells expressing the CEA and/or MUC1 may represent a potential partner for the creation of DC/tumor fusion cells targeting induction of antigen-specific CTL responses. Our report demonstrates the simultaneous induction of CRCA-specific CTL responses restricted by HLA-A2 and -A24.