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ABSTRACT: :Background/Aims: The aim of this study was to investigate the impact of preoperative serum C-reactive protein (CRP) level as a prognostic indicator in patients with colorectal carcinoma (CRC). Methodology: We investigated the correlation between preoperative CRP level and clinicopathological factors including prognosis of 167 patients who underwent resection for CRC retrospectively. Clinicopathological variables were compared between patients with serum CRP levels >1mg/dL (29 patients; high-CRP group) and patients with serum CRP levels <1mg/dL (138 patients; low-CRP group). Results: In high-CRP group, 9 patients were stage I+II and 20 patients ware stage III+IV. In low-CRP group, 93 patients were stage I+II and 45 patients were stage III+IV. There were significant differences in the clinical stage, tumor diameter, curativity, final stage between the two groups (p<0.01). The overall survival and recurrence-free survival rates in high-CRP group were lower compared with the rates in low-CRP group (p<0.05 and p=0.14). In addition, the overall survival rate in stage I+II patients with high-CRP was significantly lower than that in patients with low-CRP (p<0.05). Using multivariate analysis, the preoperative elevation of serum CRP level was an independent prognostic factor in patients with CRC (p<0.05). Conclusions: We found that the preoperative elevation of serum CRP to be an independent prognostic indicator of CRC.
Hepato-gastroenterology 05/2013; 60(123). · 0.66 Impact Factor
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Chie Takasu,
Mitsuo Shimada,
Nobuhiro Kurita,
Takashi Iwata,
Hirohiko Sato, Masanori Nishioka,
Shinya Morimoto,
Kozo Yoshikawa,
Tomohiko Miyatani,
Hideya Kashihara,
Tohru Utsunomiya,
Hisanori Uehara
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ABSTRACT: BACKGROUND: Chemoradiotherapy (CRT) has been used to improve local control and survival in patients with advanced rectal carcinoma. However, a significant proportion of patients show poor response to adjuvant CRT. We thus investigated the usefulness of survivin expression as a predictive marker of the CRT response and its characteristics. METHODS: Forty-three patients with lower rectal cancer who underwent CRT were investigated. All patients received preoperative CRT consisting of TS-1 concurrent with 40 Gy of pelvic irradiation followed by curative resection. The relationship between clinical response, or pathological response, and the expression of survivin of pre-CRT biopsy specimens was evaluated by immunohistochemistry and compared with post-CRT expression. RESULTS: Positive expression of survivin was observed in 26 of 43 patients (60 %) in pre-CRT specimens. Survivin was positively expressed in 77 % of stable disease cases, and 43 % of partial response (p < 0.05). Regarding the correlation between pathological response and survivin expression, positive expression of survivin was recognized in 75 % (18 of 24) of Grade 0 + 1 cases, 50 % (7 of 14) of Grade 2 cases, and 20 % (1 of 5) of Grade 3 cases. A reverse correlation was recognized between pathological responses and survivin expression (p < 0.05). There were differences in the tumor differentiation between the survivin-positive group and the negative group (p < 0.05). The expression concordance rate was 66 % between pre- and post-CRT tissues. In post-CRT tissues, nuclear survivin expression disappeared completely and cytoplasmic expression increased, especially in responder cases. CONCLUSION: Survivin expression in biopsy could be an important predictive factor of preoperative CRT response.
International Journal of Clinical Oncology 08/2012; · 1.41 Impact Factor
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ABSTRACT: Laparoscopic skills training is becoming the standard for educating surgical residents. Because of the specific procedure which differs from that of open surgery, it is imperative to establish a unique training system to promote efficiency of learning laparoscopic skills. The aim of this study was to evaluate the efficiency of learning laparoscopic skills with or without authorized experts of JSES.
Among 71 patients who underwent laparoscopic colectomy from 2004 to 2009, 30 patients who underwent operation in introduction era without a technical expert (2004-2006), 17 patients who underwent operation in late period of introduction era without a technical expert (2006-2008), 12 patients who underwent operation by resident with technical expert (2008-2009) and 12 patients who underwent operation by technical expert, were investigated. Operative time, amount of blood loss, intra- and post-operative complications and conversion to open surgery were investigated.
Operative time: 477:333:262:220 minutes (early period:late period:resident:expert), amount of blood loss: 494:73:21:20mL and complications: ileus: 0:1:0:0, leakage: 1:1:3:0, neurological disturbance: 2:1:0:0.
Instruction by authorized technical experts of JSES is helpful to avoid pitfalls which are not seen in open surgery without an expert.
Hepato-gastroenterology 07/2012; 59(117):1412-4. · 0.66 Impact Factor
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ABSTRACT: Tumor hypoxia has been considered to be a potential therapeutic target, because hypoxia is a common feature of solid tumors and is associated with their malignant phenotype. In the present study, we investigated the antitumor effect of a novel hypoxic cytotoxin, 3-[2-hydroxyethyl(methyl)amino]-2-quinoxalinecarbonitrile 1,4-dioxide (TX-2098) in inhibiting the expression of hypoxia inducible factor-1α (HIF-1α), and consequently vascular endothelial cell growth factor (VEGF) expression in pancreatic cancer. The antitumor effects of TX-2098 under hypoxia were tested against various human pancreatic cancer cell lines using WST-8 assay. VEGF protein induced pancreatic cancer was determined on cell-free supernatant by ELISA. Moreover, nude mice bearing subcutaneously (s.c.) or orthotopically implanted human SUIT-2 were treated with TX-2098. Tumor volume, survival and expression of HIF-1 and associated molecules were evaluated in treatment versus control groups. In vitro, TX-2098 inhibited the proliferation of various pancreatic cancer cell lines. In s.c model, tumors from nude mice injected with pancreatic cancer cells and treated with TX-2098 showed significant reductions in volume (P<0.01 versus control). Quantitative real-time reverse transcription-PCR analysis revealed that TX-2098 significantly inhibited mRNA expression of the HIF-1 associated molecules, VEGF, glucose transporter 1 and Aldolase A (P<0.01 versus control). These treatments also prolong the survival in orthotopic models. These results suggest that the effect of TX-2098 in pancreatic cancer might be correlated with the expression of VEGF and HIF-1 targeted molecules.
Experimental Cell Research 03/2012; 318(13):1554-63. · 3.58 Impact Factor
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ABSTRACT: Background/Aims: Preoperative chemoradiation therapy (CRT) for advanced rectal cancer allows anal sphincter preservation in some patients who would require an abdominoperineal resection. But adequate distal margin in patients with locally advanced rectal cancer requiring preoperative CRT is unclear. The objective was to evaluate necessary distal margin from reduced tumor by preoperative CRT for anal sphincter preservation. Methodology: This study included 11 consecutive patients who performed low anterior resection and abdominoperineal resection for rectal cancer after preoperative CRT. Distal margin length from reduced tumor by preoperative CRT to residual viable cancer, tumor grade, lymph-node-metastasis stage and pathological changes of tumors were examined. Results: Length from anal side edge of reduced tumor by preoperative CRT to pathological residual tumor ranged from +6mm to -9mm. Tumor stages were as follows: T0-2, N0, M0=3, T3, N0, M0=5, T4, N0, M0=1 and T3, N0, M+1=2. Median follow-up was 19 months. Recurrence occurred in one patient and was distant and not local. Pathological examinations showed that no patient had lymph-node-metastasis and residual tumors by preoperative CRT. Conclusions: This study suggests that for patients with locally advanced rectal cancer undergoing resection and preoperative CRT, distal margins =1cm from reduced tumor by preoperative CRT seem to compromise pathological outcome.
Hepato-gastroenterology 02/2012; 59(119). · 0.66 Impact Factor
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Hirohiko Sato,
Mitsuo Shimada,
Nobuhiro Kurita,
Takashi Iwata, Masanori Nishioka,
Shinya Morimoto,
Kozo Yoshikawa,
Tomohiko Miyatani,
Masakazu Goto,
Hideya Kashihara,
Chie Takasu
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ABSTRACT: Laparoscopy-assisted gastrectomy (LAG) is becoming widely used for early gastric cancer. However, how the curability and long-term prognosis of LAG and open gastrectomy (OG) for early and advanced gastric cancer compare remains unclear. This study assessed short- and long-term outcomes after LAG with lymph node dissection in early and advanced gastric cancer.
A total of 332 patients who underwent LAG or OG for early and advanced gastric cancer from January 2001 through December 2010 were reviewed retrospectively. The mean operating time, estimated mean blood loss, number of dissected lymph nodes, and survival rates were compared between LAG and OG for early and advanced gastric cancer.
Overall, 47.6% (158/332) of patients underwent LAG; D1, D1+ lymph node dissection was carried out in 77.2%, with D2 dissection in 22.8%. Only one patient required conversion to OG. Comparing LAG and OG with D1, D1+ lymph node dissection for early gastric cancer (EGC), mean operating time was significantly longer, estimated mean blood loss was significantly smaller, and the average number of retrieved lymph nodes was significantly greater with LAG. The rate of specific postoperative morbidity was 17.2% for LAG patients and 25.0% for OG patients, with no postoperative mortality. Survival and recurrence rates were not significantly different. Comparing LAG and OG with D2 lymph node dissection for advanced gastric cancer (AGC), mean operating time was significantly longer and estimated mean blood loss was significantly smaller with LAG, while the average number of retrieved lymph nodes, specific postoperative morbidity and mortality, and survival and recurrence rates were not significantly different.
LAG with D1, D1+ lymph node dissection for EGC is safe and equivalent to open gastrectomy in curability. Moreover, LAG with D2 lymph node dissection for AGC is comparable to OG with D2 lymph node dissection with regard to short- and long-term results.
Surgical Endoscopy 02/2012; 26(8):2240-6. · 4.01 Impact Factor
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Hirohiko Sato,
Mitsuo Shimada,
Nobuhiro Kurita,
Takashi Iwata, Masanori Nishioka,
Shinya Morimoto,
Kozo Yoshikawa,
Tomohiko Miyatani,
Masakazu Goto,
Hideya Kashihara,
Chie Takasu
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ABSTRACT: Background: The safety and usefulness of the SILS-TAPP (transabdominal pre-peritoneal) procedure remain unclear. The aim of this study was to clarify the safety and usefulness of the SILS-TAPP procedure compared with standard laparoscopic TAPP and TEPP (totally extra-peritoneal pre-peritoneal) procedures. Patients and methods: 85 patients underwent laparoscopic inguinal hernia repairs (TEPP, 30 patients; TAPP, 20 patients; SILS-TAPP, 35 patients) from 2007 to 2011. The operative outcomes of the three groups were compared. Results: There was no difference in the patients' characteristics among the three groups. The TEPP Group had a longer operation time. One patient in the SILS-TAPP group had an intraoperative complication. One patient in the TAPP group had a postoperative complication, and one patient had ileus and one had an umbilical hernia in the SILS-TAPP group. The postoperative hospital stay was not significantly different among the three groups. There were no recurrences in the TEPP group, 1 case of recurrence (5.0%) in the TAPP group, and 1 case (2.9%) in the SILS-TAPP group. Conclusions: The present findings show that the SILS-TAPP repair is safe and feasible for the repair of adult inguinal hernia. J. Med. Invest. 59: 235-240, August, 2012.
The Journal of Medical Investigation 01/2012; 59(3-4):235-40.
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ABSTRACT: The inflammatory response after surgery is associated with various postoperative complications. The aim of the present prospective study was to evaluate the effects of Daikenchuto (DKT) (a Japanese herbal medicine) on the inflammatory response in patients following laparoscopic colorectal resection.
Thirty patients who underwent laparoscopic colectomy for colorectal carcinoma were divided into two groups: a DKT intake group (D group, n = 15) and a control group (C group, n = 15). The D group took 7.5 g/day of DKT from the day after surgery until the 7th postoperative day. The body temperature, heart rate, WBC count, lymphocyte count, C-reactive protein (CRP) level, β-D: -glucan level and Candida index were compared between the two groups.
The patients' mean age in the D group was significantly younger than that in the C group. D3 lymph node dissection was performed more often in the D group. The time until first flatus was significantly shorter in the D group (1.8 ± 0.5 days) than in the C group (2.7 ± 0.5 days). The CRP level was significantly lower in the D group (4.6 ± 0.6 mg/dl) than in the C group (8.3 ± 1.1 mg/dl) on the 3rd postoperative day.
Postoperative DKT administration significantly suppressed the CRP level and shortened the time until first flatus. DKT administration also significantly suppressed postoperative inflammation following surgery for colorectal cancer.
Surgery Today 12/2011; 42(7):646-51. · 1.22 Impact Factor
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Tomohiko Miyatani,
Nobuhiro Kurita,
Tohru Utsunomiya,
Takashi Iwata, Masanori Nishioka,
Kozo Yoshikawa,
Jun Higashijima,
Hideya Kashihara,
Chie Takasu,
Masakazu Fukushima,
Mitsuo Shimada
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ABSTRACT: A lot of radiosensitizers have been developed. However, there are few to be available in the clinical setting. Thymidine phosphorylase inhibitor (TPI) regulates the phosphorolysis of thymidine to thymine and 2-deoxy-d-ribose-1-phosphate which is essential for tumor angiogenesis. The aim of this study is to evaluate whether TPI augments the radiotherapy for colorectal cancer in vitro and in vivo studies.
The cytotoxicity of TPI with irradiation on HT29 and HCT116 cells was examined using MTT- and colony formation assay. At 10days post-inoculation, HT29 bearing orthotopic model mice (n=28) were divided into four groups and orally treated with TPI- (50mg/kg/day for 2weeks), radiation (RT, 2Gy×4: Total 8Gy), their combination or the vehicle. The mechanisms underlying the efficacy were assessed genomically and immunohistochemically.
Compared to each single treatment, the combination of TPI and RT synergistically inhibited the cell viability in a time- and dose-dependent manner. In the HT-29 bearing mice, the combination of TPI and RT reduced the tumor growth compared with RT alone. Notably, the mRNA levels of VEGF, TGF-β and, Rad51 and the protein expressions of VEGF and CD34 were significantly lower in the combination than the others. Furthermore, the combination markedly increased the TUNEL-positive cells, suggesting that TPI augments the cancer cell death through inhibition of angiogenesis and DNA repair system in the radiotherapy.
Our study first demonstrated that the combination of TPI and irradiation was effective in colon cancer. TPI would provide a promising therapeutic strategy as a radiosensitizer.
Cancer letters 12/2011; 318(2):199-205. · 4.86 Impact Factor
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Shinya Morimoto,
Mitsuo Shimada,
Nobuhiro Kurita,
Hirohiko Sato,
Takashi Iwata, Masanori Nishioka,
Kozo Yoshikawa,
Tomohiko Miyatani,
Hideya Kashihara,
Chie Takasu,
Hitoshi Ikushima
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ABSTRACT: S-1 based chemoradiation is the recommended treatment for rectal cancer; however, the optimal scheduling and dosing are not yet established. A Phase I study was conducted to determine the maximum tolerated dose (MTD) of S-1 with radiotherapy (RT). Endpoints were the toxicity profile of this regimen and to determine the recommended dose (RD).
Conformal RT was given using 4 fields at daily fractions of 2Gy on 5 days per week to a total dose of 40Gy. Concurrently S-1 was given twice daily throughout RT. Eligible patients had a newly diagnosed clinical stage T3-4 N0-2 M0 rectal adenocarcinoma located within 12cm of the anal verge suitable for curative resection. Surgery was performed 6 weeks from completion of preoperative chemoradiotherapy. The dose escalating from S-1 80mg/m2/day (Level 1) to 100mg/m2/day (Level 2).
Nine patients were valid for safety. In all patients, S-1 was administered. There was no dose-limiting toxicity (DLT) in patients treated at dose Level 1. Six patients were enrolled in the dose-escalation phase. At dose Level 2, two patients developed DLT and this was considered the MTD. Objective response according to RECIST were observed in 5 of 9 patients who had measurable disease (56%).
The RD of S-1 with concurrent RT was determined to be 80mg/m2/day. Preoperative RT combined with S-1 was feasible and well tolerated.
Hepato-gastroenterology 12/2011; 59(117):1428-32. · 0.66 Impact Factor
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ABSTRACT: The key anticancer agent, CPT-11 (irinotecan hydrochloride), induces severe diarrhea clinically. We investigated the effect of a Kampo medicine, Dai-kenchu-to (DKT), on CPT-11-induced intestinal injuries in rats.
Twenty-four male Wistar rats were divided into three groups: a control group; a CPT-11 group, given CPT-11 150 mg/kg intraperitoneally for 2 days; and a DKT group, given DKT 300 mg/kg orally for 5 days with CPT-11 150 mg/kg intraperitoneally on days 4 and 5. The rats were killed on day 6.
Interleukin (IL)-1β, IL-12, interferon (IFN)-γ, and tumor necrosis factor-α expression in the small intestine of the CPT-11 group was significantly higher than that of the control group. Interleukin-1β and IFN-γ expression was improved significantly by DKT (P < 0.05). The number and height of jejuna villi, injury score, and apoptosis index in the CPT-11 group were improved significantly by DKT (P < 0.05).
DKT suppressed CPT-11 induced inflammatory cytokines and apoptosis in the intestinal mucosa and maintained the mucosal integrity.
Surgery Today 11/2011; 42(1):60-7. · 1.22 Impact Factor
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ABSTRACT: Histone deacetylase 1 (HDAC1) and metastasis-associated protein 1 (MTA1) form the nucleosome remodeling and histone deacetylation (NuRD) complex and may possibly play a central role in cancer development. However, limited data has been reported regarding the expression of both HDAC1 and MTA1. The aim of the present study was to clarify the clinical role of HDAC1 and MTA1 expression in colon cancer. Seventy-four patients with colon cancer, who underwent colectomy at our institution, were enrolled in this study. Expression of HDAC1 and MTA1 was examined immunohistochemically. The patients were divided into four groups: HDAC1-positive group (n=58), HDAC1-negative group (n=16), MTA1-positive group (n=38) and MTA1-negative group (n=36). Clinicopathological factors and survival rates were compared between the groups. Regarding the clinicopathological factors, the depth of tumor invasion and stage correlated significantly with HDAC1 expression (p<0.05). Age, depth of tumor invasion and vascular invasion tended to correlate with MTA1 expression. The 5-year survival rate in the HDAC1-positive group (55.1%) was significantly worse compared to the HDAC1-negative group (86.5%) (p<0.05), and the 5-year survival rate of the MTA1-positive group (50.5%) was significantly worse than that of the MTA1-negative group (73.1%) (p=0.05). In patients with stages II-IV and curability A, B, the survival rate in those with HDAC1-positive expression was significantly worse than those with HDAC1-negative expression (p<0.05), and the survival rate of the MTA1-positive group tended to be worse than that of the MTA1-negative group (p=0.07). Overall survival in both the HDAC1 and MTA1-positive groups was significantly worse than overall survival of the other groups (p<0.05). Disease-free survival in both the HDAC1- and MTA1-positive groups, among patients with stages II-IV and curability A, B, was also significantly worse than that of the other groups (p<0.05). HDAC1 and MTA1 expression levels were significantly related to poorer prognosis. Therefore, HDAC1 and MTA1 expression levels are potential prognostic indicators for colon cancer.
Oncology Reports 08/2011; 26(2):343-8. · 1.84 Impact Factor
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ABSTRACT: After adopting preoperative assessment of the perigastric vessels using 3D-CT and standardization of the procedures, obesity still influences smooth laparoscopy assisted gastrectomy (LAG). We evaluated the impact of body mass index (BMI) and area of visceral fat tissue on the risks of LAG.
Sixty-six patients who underwent LAG for gastric cancer were included. The patients were divided into two groups by BMI (<25 BMI-L group: n = 53; ≥25 BMI-H group: n = 13) and area of intraperitoneal fat tissue (<100 cm(2) AF-L group: n = 35; ≥100 cm(2) AF-H group: n = 31), respectively. Fat scan(®), which was computer software operating on abdominal CT, was used to measure the visceral fat areas (VFA). The incidence of postoperative complications, operation time, intraoperative blood loss, and number of dissected lymph nodes were compared between each two groups.
The incidence of postoperative complications of BMI-L and BMI-H groups was 11.3% and 30%, respectively (p = 0.18). The mean blood loss was 85 and 134 g, respectively (p = 0.21). There were no significant differences in operation time and the number of retrieved LNs. The incidence postoperative complications (29%) and mean blood loss (148 g) of then VFA-H group were significantly higher than those of the VFA-L group (5.7%, 48 g). The number of retrieved LNs of the VFA-H group (n = 25) was significantly lower than that of the VFA-L group (n = 34). There was no significant difference in operation time.
In the VFA-H group, the incidence of postoperative complications and intraoperative blood loss increased, and the dissected number of LNs decreased. The area of visceral fat tissue was useful to predict risks of LAG and postoperative complications with higher precision compared with BMI.
Surgical Endoscopy 06/2011; 25(12):3825-30. · 4.01 Impact Factor
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ABSTRACT: Intraperitoneal administration of taxanes revealed excellent anti-tumor effect for peritoneal metastasis of gastric cancer in some experimental models. The aim of this study is to determine maximum tolerated dose (MTD), dose limiting toxicity (DLT) and recommended dose (RD) of intraperitoneally infused paclitaxel (PTX) with S-1 as a phase I study.
Eighteen patients with advanced gastric cancer in addition to confirmed peritoneal metastasis using laparoscopy were enrolled in this study. The regimen consists of oral administration of S-1 (Dose 80 mg: BSA<1.25 m(2), 100 mg: 1.25<BSA<1.5 m(2), 120 mg: BSA>1.5 m(2)) for 14 days and intraperitoneal infusion of PTX (Dose escalation: level I: 40, II: 60, III: 80, level IV: 90, V: 100 mg/m(2)) at day 1 and 14. PTX concentrations in serum and ascites were determined at 4, 8, 12, 24, 48 hours after the infusion, which was repeated twice every 4 weeks.
The number of patients were as follows: Level I: 3, Level II: 6, Level III: 3, Level IV: 3, Level V: 3. Grade 3 leukocytopenia was confirmed in 1 (Level II) and 2 (Level V). MTD is 90 mg/m(2), RD is 80 mg/m(2) and DLT is Grade 3 leukocytopenia. The average serum PTX concentrations remained in optimal range except for all 3 of level V patients. In all cohorts, the PTX concentrations in the ascites were approximately 1000 folds higher than those in serum for 48 hours after the infusion.
MTD and RD were PTX 90 mg/m(2), 80 mg/m(2), respectively. These findings were supported by pharmocokinetics of PTX.
The Journal of Medical Investigation 02/2011; 58(1-2):134-9.
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ABSTRACT: Oxaliplatin is now considered a standard treatment for advanced or unresectable colorectal cancer, but its main dose-limiting toxicity is sensory neuropathy. The OPTIMOX (stop and go) approach offers a reasonable strategy, but the preventive agent is not established. It is reported that the Kampo medicine, Goshajinkigan (GJG), has recently been considered an effective agent for the neuropathy of taxanes and for vibration sensation in patients with diabetic neuropathy. The aim of this study was to clarify the efficacy of GJG for peripheral neuropathy associated with oxaliplatin therapy.
From 2007, 45 patients treated with modified FOLFOX6 for non-resectable or recurrent colorectal cancer participated in the study. Twenty-two patients (GJG group) received oral administration of 7.5 g/day of GJG every day during mFOLFOX6 therapy and 23 patients (control group) did not receive GJG. Neuropathy was evaluated during every course according to DEB-NTC (Neurotoxicity Criteria of Debiopharm).
The median number of cycles per patient in the GJG group was 13 (range 4-32), and in the control group was 12 (range 4-28). The cumulative dose of oxaliplatin was 1105 mg/m(2) (GJG group) and 1120 mg/m(2) (control group). The incidence of grade 3 peripheral neuropathy in the GJG group was significantly lower than in the control group (p < 0.01, log-rank test). The incidence of grade 3 peripheral neuropathy after 10 courses was 0% in the GJG group and 12% in the control group, and after 20 courses was 33% in the GJG group and 75% in the control group. The percentage of grade 2 and 3 peripheral neuropathy in the GJG group was lower than that in the control group. There were no differences in adverse effects between the two groups except for peripheral neuropathy and influence on tumor response.
The Kampo medicine, Goshajinkigan, is useful in preventing neuropathy in non-resectable or recurrent colorectal cancer patients treated with a FOLFOX regimen.
International Journal of Clinical Oncology 01/2011; 16(4):322-7. · 1.41 Impact Factor
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ABSTRACT: Serum soluble interferon-alpha/beta receptor (sIFN-alpha/betaR) and high-sensitivity C-reactive protein (hs-CRP) levels were evaluated in the patients with gastrointestinal and hepatobiliary-pancreatic cancer. We compared the sensitivity and specificity of serum sIFN-alpha/betaR with that of serum hs-CRP and evaluated the two diagnostic parameters in combination. Serum sIFN-alpha/betaR levels were measured in 92 patients and 25 healthy individuals by enzyme-linked immunosorbent assay. The diagnoses were 37 cases of hepatocellular carcinoma, 17 cases of pancreatic cancer, 15 cases of colon cancer, 13 cases of biliary tract cancer, and 10 cases of gastric cancer. Serum levels of sIFN-alpha/betaR and hs-CRP were significantly higher in the patients than in healthy individuals (p<0.05). The optimal cut-off values of sIFN-alpha/betaR and hs-CRP were 3600pg/ml and 0.5microg/ml, respectively. The sensitivity and specificity for these thresholds were 94.6% and 88.0%, whereas positive predictive and negative predictive values were 96.7% and 81.5%. These results suggest that a combination of serum sIFN-alpha/betaR and hs-CRP thresholds may be more reliable diagnostic parameter for gastrointestinal and hepatobiliary-pancreatic cancer.
Cytokine 10/2009; 49(3):251-5. · 3.02 Impact Factor
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ABSTRACT: The activation of Hedgehog signaling, which is critical to normal mammalian gastrointestinal development, is implicated in the development of various tumors, including colorectal cancer. In the pancreas, a precursor lesion overexpresses the Sonic hedgehog (Shh) when compared with normal tissue and cancer. The present study was designed to investigate Shh related protein expression in hyperplastic polyps and the adenoma-carcinoma sequence in the colon and rectum.
Seventeen hyperplastic polyps, 24 adenomas of the colon, 69 adenocarcinomas (31 well-differentiated, 38 moderately-differentiated), and 30 normal colon samples were used in the study. We checked the expression of Shh, both patched (Ptch) and smoothened (Smo), by immunohistochemistry and compared the expression rate of each group.
Almost all adenomas, 22 of 23 (96%), expressed Shh. In other groups, 4 of 17 hyperplastic polyps (24%), 7 of 31 well-differentiated adenocarcinomas (23%), 13 of 38 moderately-differentiated adenocarcinomas (34%) and none of the 30 normal samples expressed Shh. The rate of expression in Ptch and Smo gradually increased in accordance with tumor progression.
This result indicates that Shh-related carcinogenesis and Shh expression may be a trigger for the adenoma-carcinoma sequence. This study suggests a potential therapeutic target of hedgehog blockade in carcinogenesis.
Journal of Gastroenterology 09/2009; 44(11):1113-7. · 4.16 Impact Factor
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Surgery 07/2009; 145(6):682-4. · 3.10 Impact Factor
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ABSTRACT: Background: More than two trocar ports 12 mm in diameter were usually used to remove a foreign body from the peritoneal cavity using laparoscopic surgery. We designed a method of laparoscopic removal through a single port 5 mm in diameter and a flexible cholangioscope. Patients and Methods: The patient had a ventriculoperitoneal shunt (V-P shunt) catheter implanted for hydrocephalus of unknown cause in his 40s. Endoscopic marsupialization of the third ventricle was performed because of functional failure of the V-P shunt catheter 7 years after the implantation. A falling off of the V-P shunt catheter into the pelvic space was detected, and laparoscopic removal of the V-P shunt catheter was performed. A laparoscope was inserted through a trocar port 5 mm in diameter to confirm the location of the V-P shunt catheter following replacement of the flexible cholangioscope to grasp the catheter. The catheter was held using a snare catheter through the cholangioscope. The V-P shunt catheter was removed by pulling through the trocar port with the flexible cholangioscope. Conclusion: Laparoscopic removal is a good technique for removal of a foreign body in the peritoneal cavity. It enables one-port laparoscopic removal using a flexible cholangioscope.
Digestive surgery 06/2009; 26(3):205-8. · 1.37 Impact Factor
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ABSTRACT: It is well known that hypoxic milieu is the primary cancer environment. Therefore, tumor hypoxia is considered to be a potential therapeutic target. In the present study, we investigated the antitumor and antimetastatic effect of hypoxic cell radiosensitizer, TX-1877 on xenograft model of rectal cancer.
Nude mice bearing subcutaneously or orthotopically implanted human colon cancer cell lines HCT-116 and HT-29 were treated with TX-1877, irradiation or TX-1877 with irradiation. Tumor volume, survival, expression of matrix metalloproteinase (MMP)-2, MMP-7, MMP-9 and urokinase-type plasminogen activator (uPA) and incidence of lymph node metastasis were evaluated in treatment versus control group.
In subcutaneous model, tumor treated with TX-1877 and irradiation showed significant reductions in volume (P < 0.05 vs. control, TX-1877 or irradiation group). Quantitative real-time reverse transcription-PCR and immunohistochemical analysis revealed that TX-1877 significantly inhibited expression of the MMP-9 and uPA. These treatments also inhibited the para-aortic lymph node metastasis, however, did not prolong the survival in orthotopic model.
These data show that the treatment of TX-1877 with irradiation decreased growth of human rectal cancer and, furthermore, suppressed lymph node metastasis.
Cancer Chemotherapy and Pharmacology 02/2009; 64(5):885-92. · 2.83 Impact Factor
