Fusobacterium nucleatum detected simultaneously in a pyogenic liver abscess and advanced sigmoid colon cancer.

Fusobacterium nucleatum is an invasive, adherent, and pro-inflammatory anaerobic bacterium involved in various infections and colorectal cancer. We report a case with pyogenic liver abscess, diagnosed with advanced sigmoid colon cancer, in whom F. nucleatum was simultaneously detected. In this patient, F. nucleatum was systematically analyzed using the molecular biological techniques of metagenome analysis, conventional PCR, and microbial fluorescence in situ hybridization.

[A case of unknown primary cancer responding to chemotherapy selected based on the results of an anticancer drug sensitivity test].

CASE: The patient was a 64-year-old man. In 1998, he underwent proximal gastrectomy for gastric cancer. In September 2007, follow-up CT revealed multiple tumors around the hilum of the spleen, and he was referred to our hospital. On the initial consultation, the marked retention of ascites was noted. The levels of tumor markers such as PIVKA-II and a-fetoprotein were markedly increased. Despite various examinations, the primary focus could not be determined. In November 2007, an exploratory laparotomy was performed, but the primary focus was unclear, so one of the nodules of the major omentum was excisionally biopsied. An anticancer drug sensitivity test showed that the specimen was sensitive to 5-FU and CDDP. Therefore, the combined chemotherapy with 5-FU and CDDP was performed. The patient responded to this therapy. Ascites and tumor markers remarkably decreased, and the performance status improved from 3 to 1. CONCLUSION: These results suggest the usefulness of an anticancer drug sensitivity test in the treatment of cancer in which the primary focus is unclear.

[A case report of complete response to RPMI regimen for multiple lymph node metastases following rectal cancer surgery].

A 78-year old man underwent low anterior resection for Stage IIIb rectal cancer(Ra). After surgery, he underwent the Roswell Park Memorial Institute(RPMI)regimen for 6 months followed by oral UFT for 8 months. Since liver metastasis(S6)recurred 2 years and 2 months after surgery, he underwent S6 subsegmentectomy. Four years and 4 months later, he developed multiple lymph node metastases(the Virchow, paraaortic, and intrapelvic lymph nodes), for which FOLFIRI therapy was started, but converted to the RPMI regimen because of strong gastrointestinal side effects. After 3 courses of this regimen, tumor markers returned to normal, and imaging studies showed that the metastases had disappeared. This was interpreted as a complete response(CR). The patient has maintained the complete response for 1 year and 4 months since the start of the RPMI regimen.

An anticancer drug sensitivity test to determine the effectiveness of UFT as postoperative adjuvant chemotherapy for patients with stage III colorectal cancer.

BACKGROUND: Tissue samples from patients with pathologic ((p)) stage III colorectal cancer were tested for sensitivity to 5-fluorouracil (5-FU). On the basis of the results, patients were divided into 5-FU-sensitive and 5-FU-resistant groups, and both groups were treated with fluoropyrimidine (UFT) as postoperative adjuvant chemotherapy. Recurrence, 5-year survival rates, and 5-year recurrence-free survival rates were compared. METHODS: The anticancer sensitivity test described in this study was carried out using tumor samples obtained surgically from 34 patients with curatively resectable colorectal cancer that had been diagnosed definitively as (p)stage III (IIIa, 23 patients; IIIb, 11 patients). Regardless of tumor sensitivity or resistance to 5-FU, all 34 patients were subsequently treated daily with UFT at 300 mg/day as postoperative adjuvant chemotherapy. Treatment was initiated 3 weeks after surgery and continued for 2 years. RESULTS: Of the 34 patients with (p)stage III colorectal cancer, the tumors of 16 (47%) were 5-FU-sensitive (S group) and 18 (53%) were 5-FU-resistant (R group). The recurrence rates in the S and R groups following postadjuvant therapy with UFT were 25% and 61%, respectively, which is a significantly lower response in the S group (P = .045). The odds ratio of recurrence in the R group vs. the S group was 4.71. The 5-year survival rate was 85.7% in the S group and 46.7% in the R group, but the difference was not significant (P = .066). The 5-year recurrence-free survival rate was significantly higher in the S group than in the R groups (71% vs. 32%, P = .010). According to Cox's multivariate analysis of recurrence-free survival, the sensitivity test was significantly predictive. CONCLUSION: Administration of UFT as postoperative adjuvant therapy to 5-FU-resistant patients had no significant effect on outcome.

Evaluating distribution of the left branch of the middle colic artery and the left colic artery by CT angiography and colonography to classify blood supply to the splenic flexure.

INTRODUCTION: CT angiography has gained widespread acceptance for preoperative evaluation of blood supply in patients with colorectal cancer. However, there have been few reports that pertain to the splenic flexure, for which surgery is technically difficult. We used preoperative CT angiography and CT colonography to evaluate blood supply to the splenic flexure. METHODS: We defined the splenic flexure as the junction of the distal third of the transverse colon and the proximal third of the descending colon. We reviewed 191 cases and considered the descending colon as divided into the proximal third and the distal two-thirds; we then determined which part of the descending colon the left colic artery (LCA) entered. We also considered the transverse colon as divided into the proximal two-thirds and the distal third, and evaluated which part of the transverse colon the left branch of the middle colic artery entered. RESULT: We classified blood supply to the splenic flexure into six types, described by the feeder vessels: type 1, the LCA (39.7%); type 2, the left branch of the middle colic artery (17.8%); type 3, the LCA and the left branch of the middle colic artery (9.9%); type 4, the accessory left colic artery (4.1%); type 5, the LCA and the accessory left colic artery (2.6%); and type 6, the marginal artery (25.6%). CONCLUSION: We classified blood supply to the splenic flexure into more complex types than previous reports had. Because we dissect the lymph nodes according to the type of blood supply, knowing the type before splenic flexure surgery is crucial.

Repeated hepatic intra-arterial chemotherapy based on results of anticancer drug sensitivity test in patients with synchronous hepatic metastases from colorectal cancer.

OBJECTIVE: We determined whether hepatic intra-arterial infusion of 5-fluorouracil (5-FU) in patients with synchronous hepatic metastases from colorectal cancer, in whom the primary lesion was resectable but hepatic metastatic lesions were non-resectable helped improve survival time when administered on the basis of the results of the anticancer drug sensitivity test. PATIENTS AND METHODS: The study population consisted of 29 patients with synchronous hepatic metastases from colorectal cancer who underwent surgical resection of the primary lesion alone. Of these 29 patients, 21 received hepatic intra-arterial infusion of 5-FU postoperatively after the 5-FU sensitivity test. The remaining 8 patients underwent surgical resection of the primary lesion but neither sensitivity testing nor hepatic intra-arterial chemotherapy. Tissue fragments were cultured, with each concentration of 5-FU in the thermoreversible gelation polymer forming a three-dimensional structure at 37 degrees C. The viability of tumor cells was evaluated according to WST methods; inhibitory concentration of 50% (IC50) values were calculated. We considered cancer tissue to be sensitive to IC50 values that were below twice the peak plasma concentration (120 microg/ml). RESULTS: Of the 21 patients, 10 had sensitivity to 5-FU and 11 had no sensitivity. The response rates were 90.0% and 9.1%, respectively. The median survival times were 38 months and 10 months in these groups, respectively, and 7 months in patients who received no chemotherapy. This finding indicates a significantly longer survival time in the sensitive group, compared with either the insensitive group or the no chemotherapy group (P = .0014 P = .0023). The cumulative survival rate was significantly higher in the sensitive group compared with the insensitive group (P = .0001) CONCLUSIONS: Ultimately, the group with sensitivity to 5-FU showed a significantly longer median survival time than the insensitive group.

New chemosensitivity test using a thermo-reversible gelation polymer for recurrent gynecologic cancer patients and a preliminary study of mechanisms of anticancer drug resistance.

OBJECTIVES: TGP (thermo-reversible gelation polymer) is a high molecular compound that has so-gel transmitting temperature of 221C Since solid cancer tissue grows in this polymer three-dimensionally, and fibroblasts scarcely grow in it, TGP is suitable for chemosensitivity assays for solid tumors. In this study, a chemosensitivity test using TGP was applied to recurrent gynecologic cancer patients in order to evaluate its utility and efficacy. In some ovarian cancer cases, expression of anticancer drug resistance-related proteins was also analyzed. METHODS: Recurrent tumor tissues were surgically obtained with informed consent. After these tissues were minced and incubated for 4 days with CDDP, mitomycin C, 5-fluorouracil, paclitaxel, and CPT-11, the sensitivity against these drugs was estimated. Western blotting was performed in 8 recurrent ovarian cancer tissues in order to analyze the expression of Bcl-2, MRP2, BCRP, and GST-pi. RESULTS: The total evaluability rate of this assay was 90.6% (29/32). Sensitive drugs could be determined in 5 of 7 ascites samples (71.4%) and in 2 of 3 intra-tumoral fluid samples (66.7%). The overall clinical response rate of chemotherapy determined by these results was 50.0%. There were significant correlations between the IC50 of CDDP and Bcl-2, BCRP, GST-pi, and between that of 5-FU and MRP 2. CONCLUSIONS: Although this was a preliminary study, the chemosensitivity test using this new material appears to be useful for designing 'made-to order' salvage chemotherapy for pretreated recurrent gynecologic patients. In order to overcome multidrug resistance, the mechanisms of multidrug resistance should be further investigated.

Appendiceal Abscesses Reduced in Size by Drainage of Pus from the Appendiceal Orifice during Colonoscopy: A Report of Three Cases.

Interval appendectomy (IA) for appendiceal abscesses is useful for avoiding extended surgery and preventing postoperative complications. However, IA has problems in that it takes time before an abscess is reduced in size in some cases and in that elective surgery may result in a delay in treatment in patients with a malignant tumor of the appendix. In order to rule out malignancy, we performed colonoscopy on three patients with an appendiceal abscess that did not decrease in size 5 or more days after IA. After malignancy had been ruled out by examination of the area of the appendiceal orifice, the appendiceal orifice was compressed with a colonoscope, and a catheter was inserted through the orifice. Then, drainage of pus was observed from the appendiceal orifice into the cecal lumen. Computed tomography performed 3 days after colonoscopy revealed a marked reduction in abscess size in all patients. No endoscopy-related complication was noted. Colonoscopy in patients with an appendiceal abscess may not only differentiate malignant tumors, but also accelerate reduction in abscess size.

A new chemosensitivity assay for ascites tumor cells using a thermoreversible gelation polymer as a culture medium and the observed clinical responses.

BACKGROUND/AIM: Ascites tumor cells from patients with peritonitis carcinomatosa were tested for cis-diamminedichloroplatinum (CDDP) sensitivity. The patients were divided into CDDP-sensitive and resistant groups. Survival and time to progression (TTP) rates were compared. MATERIALS AND METHODS: 18 peritonitis carcinomatosa patients with class V ascites based on cytologic diagnosis were enrolled in this study. Chemosensitivity testing of the ascites tumor cells was done to determine their sensitivity to CDDP using a three-dimensional culture matrix of thermoreversible gelation polymer (TGP). CDDP at a dose calculated to achieve ascitic fluid drug levels equivalent to the IC(50) was given intraperitoneally to 12 CDDP-sensitive patients and 6 CDDP-resistant patients. RESULTS: Both the median survival time and the median TTP were significantly longer in CDDP-sensitive patients than in CDDP-resistant patients (survival time 105 vs. 13 days, p = 0.019; TTP 90 vs. 5 days, p = 0.029). CONCLUSION: The results indicate the potential feasibility of controlling ascites in cancer patients in whom a maximal dose effect can be achieved with a minimal dose of chemotherapy.

The role of HMGB-1 on the development of necrosis during hepatic ischemia and hepatic ischemia/reperfusion injury in mice.

BACKGROUND: High-mobility group 1 (HMGB-1) is a late mediator of endotoxin lethality in mice. The release of HMGB-1 is delayed compared to other proinflammatory cytokines that mediate shock and tissue injury. The purpose of this study was to investigate the role of HMGB-1 levels in response to hepatic ischemia, hepatic I/R injury, and the relationship between changes in HMGB-1 and other cytokines. MATERIALS AND METHODS: Three murine models were employed: our robust model of segmental hepatic warm ischemia (SHWI), a model of partial hepatic ischemia/reperfusion injury (PHIRI), and a model of total hepatic ischemia/reperfusion injury (THIRI). Over a 48-h period following ischemic insult and reperfusion using these models, serum HMGB-1 concentrations, concentrations of HMGB-1 in ischemic and nonischemic lobes, and serum concentrations of TNF-alpha and IL-6 levels were determined in mice. An anti-HMGB-1 antibody treatment was used in SHWI and THIRI to evaluate what aspects of response to ischemia and reperfusion were potentially mediated by HMGB-1. RESULTS: Hepatic HMGB-1 tissue concentrations exhibited biphasic changes in SHWI mice, which were increased in the ischemic lobes relative to nonischemic lobes at 12 h but decreased relative to nonischemic lobes at 24 h after ischemic insult. These results suggested that HMGB-1 was released into the systemic circulation by necrotic cells over the first 12 h but this process may be complete by 24 h postischemia. By 6 to 12 h after SHWI, serum TNF-alpha began to increase significantly and continued to increase for 18 h, followed by a sudden decline. Similarly, serum IL-6 increased over 1-3 h after SHWI and then decreased over the next 6 h. Treatment with an anti-HMGB-1 antibody significantly prolonged survival time in SHWI and THIRI. CONCLUSIONS: HMGB-1 plays a significant role in the response to hepatic ischemia and hepatic ischemia/reperfusion injury. The present study demonstrated a time-dependent production of HMGB-1 following hepatic warm ischemia in mice. The inherent HMGB-1 in ischemic areas was exhausted and HMGB-1 may be released by necrotic cells. HMGB-1 activation is involved in immediate proinflammatory stress response to I/R and anti-HMGB-1 antibody treatment remarkably improved survival. We demonstrated that systemic HMGB-1 accumulation was measured at an earlier phase of the hepatic ischemia and ischemia/reperfusion injury model than LPS-induced endotoxemia.

A new method to prepare multicellular spheroids in cancer cell lines using a thermo-reversible gelation polymer.

The purpose of this study is to utilize the thermo-reversible gelation polymer in which the sol-gel transitting phase is reversibly changed by temperature in a three-dimensional culture system. Human cancer cells have been observed to form multicellular spheroids, whereas fibroblasts slowly develop into small spheroids with the culture medium including this polymer. This polymer has some advantages for use as a culture material, as follows: first, cancer cells grow three-dimensionally in the aqueous solution of this polymer; second, it is easy to harvest cells or spheroids in the aqueous solution of this polymer by simply cooling down the temperature; and third, the culture medium including this polymer is so translucent that the cells or spheroids can be observed through a phase-contrast microscope. We thus conclude that this polymer is a very useful material for three-dimensional cultures.