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author:("Kitano, seiko")
1.  Incidence and predictors of adenocarcinoma following endoscopic ablation of Barrett’s esophagus 
Digestive diseases and sciences  2014;59(7):1560-1566.
The rate and risk factors of recurrent or metachronous adenocarcinoma following endoscopic ablation therapy in patients with Barrett’s esophagus (BE) have not been specifically reported.
The aim of this study was to determine the incidence and predictors of adenocarcinoma after ablation therapy for BE high-grade dysplasia (HGD) or intramucosal carcinoma (IMC).
This is a single center, retrospective review of prospectively collected data on consecutive cases of endoscopic ablation for BE. A total of 223 patients with BE (HGD or IMC) were treated by ablation between 1996 and 2011. Primary outcome measures were recurrence and new development of adenocarcinoma after ablation. Recurrence was defined as the presence of adenocarcinoma following the absence of adenocarcinoma in biopsy samples from 2 consecutive surveillance endoscopies. Logistic regression analysis was performed to assess predictors of adenocarcinoma after ablation.
183 patients were included in the final analysis, and 40 patients were excluded: 22 for palliative ablation, 8 lost to follow-up, 5 for residual carcinoma and 5 for postoperative state. Median follow-up was 39 months. Recurrence or new development of adenocarcinoma was found in 20 patients (11%) and the median time to recurrence/development of adenocarcinoma was 11.5 months. Independent predictors of recurrent or metachronous adenocarcinoma were hiatal hernia size ≥ 4cm (odds ratio 3.649, P = 0.0233) and histology (HGD/adenocarcinoma) after 1st ablation (odds ratio 4.141, P = 0.0065).
Adenocarcinoma after endoscopic therapy for HGD or IMC in BE is associated with large hiatal hernia and histology status after initial ablation therapy.
PMCID: PMC4071117  PMID: 24395382
Barrett’s esophagus; Adenocarcinoma; Recurrence; Ablation techniques; Endoscopy
2.  Establishment of new predictive markers for distant recurrence of colorectal cancer using lectin microarray analysis 
Cancer Medicine  2014;4(2):293-302.
We evaluated the clinical benefits of novel predictive markers for distant recurrence with colorectal cancer using lectin microarray analysis of cell surface glycan modifications. Glycoproteins were extracted from formalin-fixed, paraffin-embedded tumor specimens and normal epithelium from 53 consecutive curatively resected stage I–III colorectal cancer cases and then subjected to lectin microarray to obtain lectin–glycan interaction (LGI) values. In addition, clinicopathological factors associated with distant recurrence were identified. LGI values that were associated with distant recurrence were validated with an additional 55 curatively resected stage II colorectal cancer cases. LGI values for Agaricus bisporus (ABA) lectin, prominent in cancer tissues, were statistically associated with distant recurrence. ABA lectin staining exhibited strikingly intense signals in the cytoplasm and apical surfaces of cancer cells, while weak staining was observed in the supranuclear regions of normal epithelium. This ABA tumor/normal LGI ratio may be a new predictive biomarker for distant recurrence of curatively resected colorectal cancer.
PMCID: PMC4329012  PMID: 25355679
Colorectal cancer; glycoprotein; lectin; prediction; recurrence
3.  A Novel Anti-Histone H1 Monoclonal Antibody, SSV Monoclonal Antibody, Improves Lung Injury and Survival in a Mouse Model of Lipopolysaccharide-Induced Sepsis-Like Syndrome 
BioMed Research International  2015;2015:491649.
Background. Histones play important roles in both host defenses and inflammation related to microbial infection. A peptide mimotope (SSV) was identified from a novel histone H1 monoclonal antibody (16G9 mAb) that was shown to inhibit the mixed lymphocyte reaction. In the present study, an anti-SSV producing hybridoma was established. We investigated the effects of SSV mAb in a mouse acute inflammation model induced by intraperitoneal injection of lipopolysaccharide (LPS). Methods. SSV mAb was generated and characterized. Mice were treated with SSV mAb or a control IgG antibody prior to LPS injection. Evaluation of survival rate and lung tissue on histological score was performed. The levels of inflammatory cytokines and histones H1, H3, and H4 in plasma and lung tissue were measured by ELISA. Results. Competitive ELISA revealed that SSV mAb binds to histone H1. SSV mAb improved lung injury and prolonged the survival of LPS-injected mice. Increased levels of histones H1, H3, and H4 and inflammatory cytokines (TNF-α, IL-1β, and IL-6) in plasma and lung tissue after LPS injection were ameliorated by SSV mAb. Conclusion. SSV mAb is shown to have anti-inflammatory activity and organ-protective effects, highlighting the importance of controlling histone H1 as well as H3 and H4 levels during inflammation.
PMCID: PMC4306253  PMID: 25649890
4.  Effect of the new synthetic vitamin E derivative ETS-GS on radiation enterocolitis symptoms in a rat model 
Oncology Letters  2013;6(5):1229-1233.
Radiation enterocolitis is a severe adverse event that occurs after radiotherapy for malignant abdominal tumors. In this study, the therapeutic effects of ETS-GS, a novel vitamin E derivative with antioxidative and anti-inflammatory abilities, were examined in a rat model of radiation enterocolitis. The radiation enterocolitis model was created by irradiation of male rats with a single dose of 10 Gy. ETS-GS was administered subcutaneously (10 mg/kg/day) for five consecutive days from two days prior to irradiation. The animals were sacrificed three days after irradiation; following which, ileal tissue samples were analyzed for macroscopic and histological findings, presence of apoptosis, degree of oxidative stress and inflammation. In the irradiated group, severe erosion was observed in the small intestine in addition to necrosis of the mucosal layer, swelling and invasion of inflammatory cells of the submucosal layer, and shortening of the crypts. In irradiated rats that received ETS-GS, mucosal injury in the small intestine was milder compared with that of irradiated rats that received no ETS-GS. In addition, ETS-GS decreased apoptosis in the small intestine and reduced the activity of myeloperoxidase and malondialdehyde, which are markers for inflammation and oxidative stress. ETS-GS with antioxidant activity has a therapeutic effect on the symptoms of radiation enterocolitis in a rat model.
PMCID: PMC3813668  PMID: 24179500
radiation enterocolitis; vitamin E derivative; apoptosis
5.  Safety and effectiveness of mechanical versus hand suturing of intestinal anastomoses in an animal model of peritonitis 
Mechanical stapling for colorectal anastomosis is popular, but the safety of its use for anastomosis in peritonitis is unclear. We evaluated the safety and effectiveness of mechanically stapled vs. hand-sutured anastomosis by comparing wound healing in an animal model of bacterial peritonitis. Male Sprague-Dawley (n=48) rats underwent cecal ligation and puncture. After 24 h, rats were divided into two groups: the stapler group (cecal resection with mechanical stapler, n=24) and the hand-sutured group (cecal resection and stump closure with surgical absorbable suture, n=24). Anastomotic segments were excised and as indicators of wound healing, anastomotic bursting pressure (ABP) and tissue hydroxyproline concentration were determined over time. After harvesting, anastomotic segments were analyzed by quantitative real-time polymerase chain reaction (PCR) to determine relative expression of transforming growth factor-β1 (TGF-β1) and vascular endothelial growth factor (VEGF) normalized to that of a constitutive gene. The operative time was significantly shorter in the stapler vs. the hand-sutured group. Both groups showed progressive increases in ABP over the postoperative period. ABP was significantly higher in the stapler vs. the hand-sutured group on postoperative days (PODs) 0 and 3. Tissue hydroxyproline concentration increased from POD 7 in both groups, but between-group difference was not significant. Both groups showed progressive increases in TGF-β1 and VEGF expression during the 7-day postoperative period. On POD 5, TGF-β1 gene expression was higher in the stapler vs. the hand-sutured group. VEGF gene expression was identical in both groups. In conclusion, anastomosis by stapler is safer and more effective than that by hand suturing in bacterial peritonitis, since it requires less operating time and creates stronger anastomoses in the early postoperative period.
PMCID: PMC3439102  PMID: 22970027
wound healing; intestinal anastomosis; mechanical stapler; hand suture
6.  Biological predictors of survival in stage II colorectal cancer 
Molecular and Clinical Oncology  2013;1(4):643-648.
The routine use of postoperative adjuvant chemotherapy in patients with stage II colorectal cancer is not recommended. However, the incidence of tumor recurrence or distant metastasis in these patients is reported to be 25–35%. The identification of high-risk patients with stage II colorectal cancer remains difficult. Therefore, the aim of this study was to determine the risk factors that may help identify stage II colorectal cancer patients with unfavorable prognosis. Paraffin-embedded tissue samples from 109 patients with stage II colorectal cancer following curative operation were analyzed. Thirteen clinicopathological variables and 5 biological markers were assessed using immunohistochemistry, including p53 (tumor suppressor gene), CD10 (tumor invasion marker), CD34 (angiogenic marker), Ki-67 (cell proliferation index) and CAM 5.2 (marker of lymph node micrometastasis) and investigated for associations with disease-specific survival. Univariate analysis revealed bowel obstruction, lymph node micrometastasis and lymphatic invasion (P<0.01) to be highly significant factors for determining the 5-year disease-specific survival. By contrast, the multivariate analysis revealed lymph node micrometastasis and lymphatic invasion to be independent prognostic factors. Stage II colorectal cancer patients with lymph node micrometastasis and lymphatic invasion may therefore be suitable candidates for adjuvant chemotherapy to improve prognosis.
PMCID: PMC3915554  PMID: 24649222
colorectal cancer; prognostic factor; lymphatic invasion; lymph node micrometastasis
7.  Poor Prognosis of Advanced Gastric Cancer with Metastatic Suprapancreatic Lymph Nodes 
Annals of Surgical Oncology  2013;20(7):2290-2295.
Whether gastrectomy with D2 lymphadenectomy improves survival of patients with advanced gastric cancer (AGC) remains controversial. Few studies have described the pathological features of AGC with metastatic suprapancreatic lymph nodes (LN), which are the target of D2 lymphadenectomy. This study therefore aims to clarify the prognosis and clinical pathological features including the number and location of metastatic LN in AGC with metastatic suprapancreatic LN.
406 patients with AGC, who underwent gastrectomy with D2 lymphadenectomy from 1982 to 2007 at Oita University, were reviewed retrospectively with regard to presence or absence of metastatic suprapancreatic LN. The pathological factors associated with AGC with metastatic suprapancreatic LN were examined by univariate and multivariate analysis.
Of 362 patients with AGC, 78 had suprapancreatic LN metastasis (21.5 %), differing significantly in terms of presence of vascular invasion and having a larger number of metastatic perigastric LN in comparison with only metastatic perigastric LN on univariate analysis. According to multivariate analysis, they were associated with presence of vascular invasion and a large number of total metastatic LN (more than two; N2≤). The overall 5-year survival rate of the AGC with perigastric LN metastasis (station 1–7) group was 37.9 % and of the AGC with suprapancreatic LN metastasis group was 12.8 %. There were significant differences in each group (P < 0.05).
Patients with AGC with metastatic suprapancreatic LN had a large number of total metastatic LN and poor prognosis, suggesting that it may be a systemic disease.
PMCID: PMC3675275  PMID: 23299769
8.  Two-stage laparoscopic resection of colon cancer and metastatic liver tumour 
We report herein the case of 70-year-old woman in whom colon cancer and a synchronous metastatic liver tumour were successfully resected laparoscopically. The tumours were treated in two stages. Both post-operative courses were uneventful, and there has been no recurrence during the 8 months since the second procedure.
PMCID: PMC3523454  PMID: 23248444
Colorectal cancer; laparoscopic hepatectomy; laparoscopy-assisted colectomy; metastatic liver tumor; two-stage procedure
9.  Expression of Matrix Metalloproteinase-7 is an Unfavorable Prognostic Factor in Intrahepatic Cholangiocarcinoma 
Intrahepatic cholangiocarcinoma (IHCC) is a highly malignant neoplasm, but the prognostic factors of IHCC are not yet fully understood. The matrix metalloproteinases (MMPs) are known to be related to tumor viability. The aim of this study was to evaluate the prognostic significance of clinicopathological and immunohistochemical characteristics of resected IHCC.
Patients and Methods
From 1996 to 2006, we surgically treated 35 patients with IHCC. Clinicopathological and immunohistochemical characteristics, including expression of MMPs, vascular endothelial growth factor, and epidermal growth factor receptor in the resected specimens, were investigated, and overall survival rates were evaluated with regard to the characteristics using univariate and multivariate analyses.
Univariate analysis revealed the significant prognostic factors to be preoperative serum CEA and CA19-9, intraoperative transfusion, tumor size, surgical margin, lymph node metastasis, invasion of portal and hepatic vein, intrahepatic metastasis, UICC stage, and expression of MMP-7. Subsequent multivariate analysis indicated that MMP-7 was an independent prognostic factor (hazard ratio (HR), 4.698; 95% confidence interval (CI), 0.057–0.866; P = 0.03) along with intrahepatic metastasis (HR, 5.694; 95% CI, 0.029–0.706; P = 0.017).
MMP-7 expression is associated with a poor prognosis in patients with resected IHCC.
PMCID: PMC3308001  PMID: 22246855
Cholangiocarcinoma; Matrix metalloprotease; Matrix metalloprotease-7; Prognostic factor
10.  Operative Timing of Laparoscopic Cholecystectomy for Acute Cholecystitis in a Japanese Institute 
These authors suggest that the best timing of laparoscopic cholecystectomy for acute cholecystitis in Japan may be within 24 hours of the onset of the disease.
Background and Objectives:
In patients with acute cholecystitis who cannot undergo early laparoscopic cholecystectomy (within 72 hours), 6 weeks to 12 weeks after onset is widely considered the optimal timing for delayed laparoscopic cholecystectomy. However, there has been no clear consensus about it. We aimed to determine optimal timing for delayed laparoscopic cholecystectomy for acute cholecystitis.
Medical records of 100 patients who underwent standard laparoscopic cholecystectomy were reviewed retrospectively. Patients were divided into group 1, patients undergoing laparoscopic cholecystectomy within 72 hours of onset; group 2, between 4 days to 14 days; group 3, between 3 weeks to 6 weeks; group 4, >6 weeks.
No significant differences existed between groups in conversion rate to open surgery, operation time, blood loss, or postoperative morbidity, and hospital stay. However, total hospital stay in groups 1 and 2 was significantly shorter than that in groups 3 and 4 (P<.01). In addition, the total hospital stay in group 3 was also significantly shorter than that in group 4 (P<.01).
Best timing of laparoscopic cholecystectomy for acute cholecystitis may be within 72 hours, and the delayed timing of laparoscopic cholecystectomy in patients who cannot undergo early laparoscopic cholecystectomy is probably as soon as possible after they can tolerate laparoscopic cholecystectomy.
PMCID: PMC3407460  PMID: 22906333
Acute cholecystitis; Laparoscopic cholecystectomy; Operation timing
12.  Lymph Node Metastasis of Gastric Cancer 
Cancers  2011;3(2):2141-2159.
Despite a decrease in incidence in recent decades, gastric cancer is still one of the most common causes of cancer death worldwide [1]. In areas without screening for gastric cancer, it is diagnosed late and has a high frequency of nodal involvement [1]. Even in early gastric cancer (EGC), the incidence of lymph node (LN) metastasis exceeds 10%; it was reported to be 14.1% overall and was 4.8 to 23.6% depending on cancer depth [2]. It is important to evaluate LN status preoperatively for proper treatment strategy; however, sufficient results are not being obtained using various modalities. Surgery is the only effective intervention for cure or long-term survival. It is possible to cure local disease without distant metastasis by gastrectomy and LN dissection. However, there is no survival benefit from surgery for systemic disease with distant metastasis such as para-aortic lymph node metastasis [3]. Therefore, whether the disease is local or systemic is an important prognostic indicator for gastric cancer, and the debate continues over the importance of extended lymphadenectomy for gastric cancer. The concept of micro-metastasis has been described as a prognostic factor [4-9], and the biological mechanisms of LN metastasis are currently under study [10-12]. In this article, we review the status of LN metastasis including its molecular mechanisms and evaluate LN dissection for the treatment of gastric cancer.
PMCID: PMC3757408  PMID: 24212800
gastric cancer; lymph node metastasis; lymph node dissection
13.  Cancer stem cell-related factors are associated with the efficacy of pre-operative chemoradiotherapy for locally advanced rectal cancer 
Pre-operative chemoradiotherapy (CRT) is an important neoadjuvant therapy for locally advanced rectal cancer. In the present study, we investigated the factors that influence the efficacy of pre-operative CRT in locally advanced rectal cancer. We divided 50 patients with locally advanced rectal carcinoma treated with pre-operative CRT into two groups according to the grade of tumor response to pre-operative CRT: low-sensitivity group and high-sensitivity group. As candidates for the prediction of sensitivity to pre-operative CRT, clinicopathological factors and 12 biomarkers, including factors related to tumor growth, cell cycle, apoptosis, tumor stroma and cancer stem cells, were examined immunohistochemically in 48 resected specimens. Thirty-one tumors showed high sensitivity and 19 showed low sensitivity to pre-operative CRT. The status of stem cell-related factors, CD133 and CD24, was significantly associated respectively with sensitivity to pre-operative CRT (P=0.003, P=0.029). In 10 tumors positive for both CD133 and CD24, low sensitivity to CRT was found in 9 (90%), whereas in 16 tumors negative for both CD133 and CD24, low sensitivity was found in 3 (19%). Other pathological parameters were not associated with tumor response to pre-operative CRT. In conclusion, overexpression of cancer stem cell-related factors, CD133 and CD24, is associated with the sensitivity of locally advanced rectal cancer to pre-operative CRT.
PMCID: PMC3440736  PMID: 22977526
rectal cancer; pre-operative chemoradiotherapy; cancer stem cell; CD133; CD24
14.  Direct invasion to the colon by hepatocellular carcinoma: Report of two cases 
Although hepatocellular carcinoma (HCC) is a common tumor, direct invasion of the gastrointestinal tract by HCC is uncommon. Recently, we encountered two cases of HCC with direct invasion to the colon. The first patient was a 79-year-old man who underwent transarterial chemo-embolization (TACE) for HCC 1.5 years prior to admission to our hospital. Computed tomography (CT) showed a 7.5-cm liver tumor directly invading the transverse colon. Partial resection of the liver and transverse colon was performed. The patient survived 6 mo after surgery, but died of recurrent HCC. The second patient was a 69-year-old man who underwent TACE and ablation for HCC 2 years and 7 months prior to being admitted to our hospital for melena and abdominal distension. CT revealed a 6-cm liver tumor with direct invasion to the colon. The patient underwent partial resection of the liver and right hemicolectomy. The patient recovered from the surgery. But, unfortunately, he died of liver failure due to liver cirrhosis one month later. Although the prognosis of HCC that has invaded the colon is generally poor due to the advanced stage of the disease, surgical resection may be a favorable treatment option in patients with a good general condition.
PMCID: PMC2731292  PMID: 18680245
Hepatocellular carcinoma; Colon; Hepatoma
15.  Laparoscopic gastric partitioning gastrojejunostomy for an unresectable duodenal malignant tumor 
As a palliative bypass for unresectable gastric or periampullary cancer, gastrojejunostomy (GJ) is sometimes associated with postoperative delayed gastric emptying. We report the successful laparoscopic application of this procedure in a 78-year-old man with duodenal obstruction. Computed tomography revealed a mass in the duodenum along with multiple masses in the liver. A radiological image showed an ulcerative tumour in the third portion of the duodenum occluding the lumen. He was diagnosed as having an unresectable duodenal cancer with multiple liver metastases. He needed palliative bypass surgery. Laparoscopically, the stomach was partially divided using an endoscopic autosuture device, and end-to-side GJ was performed successfully. He was given a normal diet on the fourth postoperative day, and there was no delayed gastric emptying. Laparoscopic gastric partitioning GJ is a feasible and safe procedure to prevent postoperative delayed gastric emptying in case of malignant duodenal obstruction.
PMCID: PMC3001169  PMID: 21188010
bypass; gastrojejunostomy; laparoscopic; palliative; unresectable
16.  Two-stage laparoscopic resection of colon cancer and metastatic liver tumour 
We report herein the case of 70-year-old woman in whom colon cancer and a synchronous metastatic liver tumour were successfully resected laparoscopically. The tumours were treated in two stages. Both postoperative courses were uneventful, and there has been no recurrence during the 8 months since the second procedure.
PMCID: PMC3016475  PMID: 21234143
Colorectal cancer; metastatic liver tumour; laparoscopic hepatectomy; laparoscopy-assisted colectomy
17.  ICG Clearance in Assessing Cirrhotic Patients with Hepatocellular Carcinoma for Major Hepatic Resection 
HPB Surgery  1997;10(3):182-183.
Objective: To deWne the safety of major hepatectomy for hepatocellular carcinoma (HCC) associated with cirrhosis and the selection criteria for surgery in terms of hospital mortality.
Design: Major hepatectomy for HCC in the presence of cirrhosis is considered to be contraindicated by many surgeons because the reported mortality rate is high (26% to 50%). Previous workers recommended that only selected patients with Child's A status or indocyanine green (ICG) retention at 15 minutes of less than 10% undergo major hepatectomy. A survery was made, therefore, of our patients with HCC and cirrhosis undergoing major hepatectomy between 1989 and 1994.
Setting: A tertiary referral center.
Patients: The preoperative, intraoperative, and post-operative data of 54 patients with cirrhosis who had major hepatectomy were compared with those of 25 patients with underlying chronic active hepatitis and 22 patients with normal livers undergoing major hepatectomy for HCC. The data had been prospectively collected.
Intervention: Major hepatectomy, defined as resection of two or more liver segments by Goldsmith and Woodburn nomenclature, was performed on all the patients. Main Outcome Measure: Hospital mortality, which was defined as death within the same hospital admission for the hepatectomy.
Results: Preoperative liver function in patients with cirrhosis was worse than in those with normal livers. The intraoperative blood loss was also higher (P=.01), but for patients with cirrhosis, chronic active hepatitis, and normal livers, the hospital mortality rates (13%, 16%, and 14%, respectively) were similar. The hospital mortality rate for patients with cirrhosis in the last 2 years of the study was only 5%. Patients with cirrhosis could tolerate up to 10 L of blood loss and survive the major hepatectomy. By discriminant analysis, an ICG retention of 14% at 15 minutes was cutoff level that could maximally separate the patients with cirrhosis with and without mortality.
Conclusion: Major hepatectomy for HCC in the presence of cirrhosis is associated with a mortality rate that is not different from the rate for patients with normal livers. An ICG retention of 14% at 15 minutes would serve as a better selection criterion than the 10% previously used.
PMCID: PMC2423851  PMID: 9174867
18.  Has Propranolol Rendered Sclerotherapy Obsolete for Poor Risk Alcoholic Cirrhotic Patients? 
HPB Surgery  1994;8(1):74-76.
PMCID: PMC2423755  PMID: 7993873

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