Impact of a board certification system and adherence to the clinical practice guidelines for gastric cancer on risk-adjusted surgical mortality after distal and total gastrectomy in Japan: a questionnaire survey of departments registered in the National Clinical Database.

PURPOSE: The relationship between board certification, clinical guideline implementation, and quality of gastric cancer surgery remains unclear. METHODS: A web-based questionnaire survey was administered to departments registered in the National Clinical Database (NCD) of Japan between October 2014 and January 2015. Quality indicators (QIs) based on the Donabedian model were evaluated. Structural QIs (e.g., affiliations with academic societies and board certifications) and process QIs (adherence to clinical practice guidelines for gastric cancer) were assessed using risk-adjusted odds ratios (AORs) for surgical mortality. Multivariable logistic regression models with a generalized estimating equation were used. RESULTS: A total of 835 departments performing 40,992 distal gastrectomies and 806 departments performing 19,618 total gastrectomies responded. Some certified institutions and physicians showed significant associations, with lower AORs for surgical mortality. Important process QIs included pre- and postoperative abdominal CT scanning, endoscopic resection based on progression, curative resection with D2 dissection for advanced gastric cancer, laparoscopic surgery, and HER2 testing for patients with unresectable recurrent gastric cancer. CONCLUSIONS: Multiple structural and process QIs are associated with surgical mortality after gastrectomy in Japan. Measuring and visualizing QIs may enhance healthcare improvements.

Geriatric Risk Prediction Models for Major Gastroenterological Surgery Using the National Clinical Database in Japan: A Multicenter Prospective Cohort Study.

OBJECTIVES: To investigate the effect of geriatric variables on 5 newly added outcomes and create risk models for predicting these outcomes. SUMMARY OF BACKGROUND DATA: Because there is a current lack of geriatric research focusing on geriatric outcomes using a national surgical database in Japan, there is a need to investigate outcomes associated with major gastro-enterological surgery using these data. METHODS: This multicenter prospective cohort study was conducted at 26 surgery departments across 21 institutions in Japan using the NCD surgical registry. in total, 22 new geriatric variables were imported from the ACS National Surgical Quality Improvement Program geriatric pilot study. The following 5 geriatric outcomes were defined: (1) postoperative delirium, (2) physical function on postoperative day 30, (3) fall risk on discharge, (4) discharge other than home with social service, and (5) functional decline on discharge, and geriatric risk prediction models for major gastroenterological surgery were created. RESULTS: Between January 2018 and December 2018, data on 3981 procedures from 7 major gastroenterological surgeries were collected and analyzed. Older age and preoperative geriatric variables (Origin status from home, History of dementia, Use of mobility aid, fall history, and not competent on admission) were strongly associated with postoperative outcomes. Geriatric risk prediction models for these outcomes were created, with C-statistic values ranging from 0.74 to 0.90, demonstrating model validity and sufficiency of fit. CONCLUSIONS: The risk models for the newly defined 5 geriatric outcomes that we created can be used in the decision-making process or provision of care in geriatric patients.

Cost of postoperative complications of lower anterior resection for rectal cancer: a nationwide registry study of 15,187 patients.

PURPOSE: To assess the increase in hospital costs associated with postoperative complications after lower anterior resection (LAR) for rectal cancer. METHODS: The subjects of this retrospective analysis were patients who underwent elective LAR surgery between April, 2015 and March, 2017, collected from a Japanese nationwide gastroenterological surgery registry linked to hospital-based claims data. We evaluated total and category-specific hospitalization costs based on the level of postoperative complications categorized using the Clavien-Dindo (CD) classification. We assessed the relative increase in hospital costs, adjusting for preoperative factors and hospital case volume. RESULTS: We identified 15,187 patients (mean age 66.8) treated at 884 hospitals. Overall, 71.8% had no recorded complications, whereas 7.6%, 10.8%, 9.0%, 0.6%, and 0.2% had postoperative complications of CD grades I-V, respectively. The median (25th-75th percentiles) hospital costs were $17.3 K (16.1-19.3) for the no-complications group, and $19.1 K (17.3-22.2), $21.0 K (18.5-25.0), $27.4 K (22.4-33.9), $41.8 K (291-618), and $22.7 K (183-421) for the CD grades I-V complication groups, respectively. The multivariable model identified that complications of CD grades I-V were associated with 11%, 21%, 61%, 142%, and 70% increases in in-hospital costs compared with no complications. CONCLUSIONS: Postoperative complications and their severity are strongly associated with increased hospital costs and health-care resource utilization. Implementing strategies to prevent postoperative complications will improve patients' clinical outcomes and reduce hospital care costs substantially.

Impact of donor and prolonged cold ischemia time of neonatal pig pancreas on neonatal pig islet transplant outcome.

BACKGROUND: Genetically modified pigs (GMP) have been developed to alleviate the shortage of donors in human islet transplantation and rejection. In this study, we characterized and compared the islets from GalTKO, GalTKO/hCD46, GalTKO/hCD46/hCD39, and wild-type (WT) neonatal pigs. METHODS: Islets were isolated from GMP and WT pig pancreases that have been packaged with ice pack for at least 24 hours. The difference in gene expression and function of islets were evaluated by microarray analysis and transplantation of islets under the kidney capsule of streptozotocin-induced diabetic immune-deficient mice, respectively. Blood glucose levels of these mice were monitored weekly post-transplantation for >100 days, and islet grafts were collected and evaluated for the presence of endocrine cells. RESULTS: The genes involved in extracellular components, cell adhesion, glucose metabolism, and inflammatory response are differentially expressed between GMP and WT pig islets. Variation in the ability of pig islets in correcting the diabetic state of the mouse recipients appears to be dependent on the pig donor. In addition, prolonged cold ischemia time had a negative effect on the transplant outcome. All normoglycemic mice were able to respond well to glucose challenge despite the initial differences in the ability of islet transplants to reverse their diabetic state. Islet xenografts of normoglycemic mice contained abundant insulin- and glucagon-positive cells. CONCLUSION: The effect of GMP and WT neonatal pig islet transplants on hyperglycemia in mice appears to be dependent on the pig donor, and prolonged cold ischemia time negatively affects the neonatal pig islet transplant outcome.

Estimates of the effects of centralization policy for surgery in Japan: does centralization affect the quality of healthcare for esophagectomies?

PURPOSE: This study compared the quality of healthcare before and after implementation of a policy restructuring the healthcare delivery system and estimated the impact of centralization. METHODS: We used the National Clinical Database to study patients undergoing esophagectomies from 2011 to 2016. We compared the effect of centralization based on the patient background, surgical mortality, and year of surgery. Difference-in-difference methods based on the generalized estimating equation logistic regression model were used for before-and-after comparisons after adjusting for patient-level expected surgical mortality. RESULTS: In total, 34,640 cases were identified. More cases with risk factors were noted in ultra-low-volume hospitals, where 38.4% of cases in underpopulated areas were treated, than in higher volume facilities, and the operative mortality, readmission within 30 days and length of stay were worse among patients treated in these hospitals. In centralized prefectures, the number of cases per hospital increased over time (7.2 in 2011 to 9.5 in 2016) while the crude operative mortality tended to decrease (3.4% in 2011 to 1.8% in 2016). The difference-in-difference estimator was 0.856 (95% confidence interval: 0.639-1.147, p = 0.298). CONCLUSION: The centralization of ultra-low-volume hospitals did not lead to a deterioration in the quality of care but rather an improving trend.

Development of gastroenterological surgery over the last decade in Japan: analysis of the National Clinical Database.

The National Clinical Database (NCD) of Japan was established in 2010 with the board certification system. A joint committee of 16 gastroenterological surgery database-affiliated organizations has been nurturing this nationwide database and utilizing its data for various analyses. Stepwise board certification systems have been validated by the NCD and are used to improve the surgical outcomes of patients. The use of risk calculators based on risk models can be particularly helpful for establishing appropriate and less invasive surgical treatments for individual patients. Data obtained from the NCD reflect current developments in the surgical approaches used in hospitals, which have progressed from open surgery to endoscopic and robot-assisted procedures. An investigation of the data acquired by the NCD could answer some relevant clinical questions and lead to better surgical management of patients. Furthermore, excellent surgical outcomes can be achieved through international comparisons of the national databases worldwide. This review examines what we have learned from the NCD of gastroenterological surgery and discusses what future developments we can expect.

[A Case of Squamous Cell Cancer of the Anus Treated with Chemoradiotherapy].

BACKGROUND: In Japan, the standard treatment for squamous cell anal cancer(SCAC)has not been established. Herein, we report a case of SCAC that completely responded to chemoradiotherapy(CRT). CASE: A woman in her 80s presented with anal pain and bleeding. Computed tomography revealed bilateral inguinal adenopathy and a tumor in the anal canal. Histopathological examination of endoscopic biopsies showed adenocarcinoma. Thus, she was diagnosed with anal canal adenocarcinoma and lymph node metastases:cT3, cN1a(No. 292), cM0, cStage Ⅲc(Japanese Classification of Colorectal, Appendiceal, and Anal Carcinoma, 9th edition). Owing to her advanced age and refusal of a stoma, CRT(S-1, mitomycin C, and radiotherapy)was administered with the expectation that salvage surgery in the form of rectal amputation would eventually be necessary. The tumor noticeably shrank after CRT. The patient is alive to this date,14 months after the final round of CRT.

[Robotic Surgery Can Complete Radical Surgery and Urinary Tract Reconstruction for Locally Advanced Rectal Cancer with Ureteral Invasion-A Case Report].

A 82-year-old man presented with diarrhea and fatigue. He had no past medical or surgical history except chronic renal failure. Locally advanced rectal cancer with invasion to left ureter was detected in computed tomography. Colonoscopy revealed a circular lesion 12 cm from the anal verge. Biopsy showed moderately differentiated adenocarcinoma. There was no sign of distal metastasis and we decided to conduct radical surgery. Robot-assisted laparoscopic lower anterior resection with partial resection of left ureter, and diverting ileostomy were carried out. Besides, urinary tract reconstruction of ureterocystoneostomy using Lich-Gregoir technique was conducted by urologists also with robot assistance. The pathological stage of the disease was pT4b(left ureter)N1bM0, pStage Ⅲc. The resection margin was secured and radical surgery was achieved. The patient was discharged on postoperative day 22nd without postoperative complication. He is alive without recurrence at 6 months after the operation.

Development of a model predicting the risk of eight major postoperative complications after esophagectomy based on 10 826 cases in the Japan National Clinical Database.

BACKGROUND: Esophagectomy is a highly invasive procedure with a high incidence of complications. The objectives of this study were to create risk prediction models for postoperative morbidity associated with esophagectomy and to test their performance using a population-based large database. METHODS: A total of 10 862 patients who underwent esophagectomy between January 2011 and December 2012 derived from the Japanese national clinical database (NCD) were included. Based on the 148 preoperative clinical variables collected, risk prediction models for eight major postoperative morbidities were created using 80% (8715 patients) of the study population and validated using the remaining 20% (2147 patients) of the patients. RESULTS: The mortality rate was 3.1% and postoperative morbidity was observed in 42.6% of the patients. The c-statistics of the eight risk models established by the training set were surgical site infection (0.564), anastomotic leakage (0.531), need for transfusion (0.636), blood loss >1000 mL (0.644), pneumonia (0.632), unplanned intubation (0.607), prolonged mechanical ventilation over 48 hours (0.614), and sepsis (0.618) in the validation analysis. CONCLUSIONS: Risk prediction models for postoperative morbidity after esophagectomy using the population-based large database showed relatively fair performance. The current models may offer baseline information for risk stratification in clinical decision makings and help select more suitable surgical and nonsurgical treatment options and future clinical studies.

Impact of a board certification system and implementation of clinical practice guidelines for pancreatic cancer on mortality of pancreaticoduodenectomy.

PURPOSES: The aim of this study was to clarify the impact of a board certification system and the implementation of clinical practice guidelines for pancreatic cancer (PC) on the mortality of pancreaticoduodenectomy in Japan. METHODS: By a web questionnaire survey via the National Clinical Database (NCD) for departments participating in the NCD, quality indicators (QIs) related to the treatment for PC, namely the board certification systems of various societies and the adherence to clinical practice guidelines for PC, were investigated between October 2014 and January 2015. A multivariable logistic regression analysis was performed to evaluate the relationship between the QIs and mortality of pancreaticoduodenectomy. RESULTS: Of 1415 departments that registered at least 1 pancreaticoduodenectomy between 2013 and 2014 in NCD, 631 departments (44.6%), which performed pancreaticoduodenectomy for a total of 11,684 cases, answered the questionnaire. The mortality of pancreaticoduodenectomy was positively affected by the board certification systems of the Japanese Society of Gastroenterological Surgery, Japanese Society of Hepato-Biliary-Pancreatic Surgery, Japanese Society of Gastroenterology, and Japanese Society of Medical Oncology as well as by institutions that used magnetic resonance imaging of ≥ 3 T for the diagnosis of PC in principle. CONCLUSIONS: The measurement of the appropriate QIs is suggested to help improve the mortality in pancreaticoduodenectomy. Masamichi Mizuma and Hiroyuki Yamamoto equally contributed.

Current status of projects for developing cancer-related clinical practice guidelines in Japan and recommendations for the future.

BACKGROUND: The current status and adoption of cancer-related clinical practice guidelines in Japan has not been elucidated yet. The purpose of this study was to propose roles and suggestions to develop future cancer-related clinical guidelines. METHODS: A questionnaire consisting of four domains with a total of 17 questions was developed. We distributed the questionnaire to 28 specific academic organizations in Japan which have developed any cancer-related clinical practice guidelines and which were funded by the Ministry of Health, Labor, and Welfare. RESULTS: Most organizations have investigated nationwide dissemination and adoption of clinical practice guidelines. The rate of adoption in clinical practice was estimated at approximately ≥ 70%. However, organizations with smaller budgets reported surveying approximately 60% of the time, whereas the ones with larger budgets reported approximately 100% success in surveying about their guidelines. The presidents of the organizations agreed that a new organization operated directly by the national government was necessary. CONCLUSION: In Japan, to develop cancer-related clinical practice guidelines, a study of clinical validation is necessary. Sufficient funds must be available to support the project to maintain and revise the guidelines. Furthermore, legal and ethical issues should be solved before establishing any registry system.

Current status of site-specific cancer registry system for the clinical researches: aiming for future contribution by the assessment of present medical care.

BACKGROUND: The current status of site-specific cancer registry has not been elucidated, but sufficient system is found in some societies. The purpose of this study was to clear the present condition of site-specific cancer registries in Japan and to suggest for the improvement. METHODS: The questionnaire was conducted by the study group of the Ministry of Health, Labor, and Welfare. It consisted of 38 questions, conflicts of interest, clinical research method, informed consent and funding for registry. We distributed this questionnaire to 28 academic societies, which had published the clinical practice guideline(s) assessed under Medical Information Network Distribution Service (MINDS). RESULTS: The concept of the importance in assessment for medical quality by the data of the site-specific cancer registry was in good consensus. But the number of the society with the mature registry was limited. The whole-year registry with the scientific researches in the National Clinical Database (NCD) and in the Translational Research Informatics Center (TRI) might seem to be in success, because assured enhancement may be estimated. Now, academic societies have the structural factors, i.e., the financial limitation in the registry maintenance and the data analysis, and in the difficulty of employment of the researchers with skill and talent. CONCLUSIONS: To manage the site-specific cancer registry effectively, the scientific registry system will be essentially important. Each academic society had much experienced highly qualified clinical researches in past. Accordingly, the scientific suggestion and co-operation should be of great importance for the improvement.

Initial verification of data from a clinical database of gastroenterological surgery in Japan.

PURPOSES: To evaluate the reliability of data collected from the gastroenterological section of the National Clinical Database of Japan (NCD), which began registrations in 2011 with ten surgical subspecialty societies. METHODS: During 2014 and 2015, 1,136,700 cases involving 115 procedures at 4374 hospitals were registered in the gastroenterological surgery section of the NCD. After a test audit using the 2014 data, 17 hospitals were selected for the first audit and data verification for 2015. The data accuracy of patient demographics, surgical outcomes, and processes was assessed using 45 items from the cases registered, in comparison with the medical records. RESULTS: In the first audit of the 2015 data, case registration accuracy verification involved 338 patients (99.4% of the extracted cases). The data accuracy with the maximum postoperative variables was > 95%. Accuracy of the mortality and status 30 days after the surgery was high (> 99%) with a sensitivity of 1.00 and a specificity of 1.00. Among the six complications studied, the recorded cases had high specificity but lower sensitivity (0.70-0.89). CONCLUSIONS: We verified the data from the gastroenterological section of the NCD and found high accuracy of data entry.

Significance of the board-certified surgeon systems and clinical practice guideline adherence to surgical treatment of esophageal cancer in Japan: a questionnaire survey of departments registered in the National Clinical Database.

BACKGROUND: It remains unknown how much institutional medical structure and process of implementation of clinical practice guidelines for esophageal cancers can improve quality of surgical outcome in Japan. METHODS: A web-based questionnaire survey was performed for departments registered in the National Clinical Database in Japan from October 2014 to January 2015. Quality indicators (QIs) including structure and process indicators (clinical practice guideline adherence) were evaluated on the risk-adjusted odds ratio for operative mortality (AOR) of the patients using registered cases in the database who underwent esophagectomy and reconstruction in 2013 and 2014. RESULTS: Among 916 departments which registered at least one esophagectomy case during the study period, 454 departments (49.6%) responded to the questionnaire. Analyses of 6661 cases revealed that two structure QIs (certification of training hospitals by Japan Esophageal Society and presence of board-certified esophageal surgeons) were associated with significantly lower AOR (p < 0.001 and p = 0.005, respectively). One highly recommended process QI regarding preoperative chemotherapy had strong tendency to associate with lower AOR (p = 0.053). In two process QIs, the answer "performed at the doctor's discretion" showed a significant negative impact on prognosis, suggesting importance of institutional uniformity. CONCLUSIONS: The medical institutional structure of board-certified training sites for esophageal surgeons and of participation of board-certified esophageal surgeons improves surgical outcome in Japan. Establishment of appropriate QIs and their uniform implementation would be crucial for future quality improvement of medical care in esophagectomy.

National survey of de novo malignancy after solid organ transplantation in Japan.

PURPOSE: In Japan, there have been no national surveys on the incidence of de novo malignancy after solid organ transplantation, which is one of the leading causes of death in transplant recipients. METHODS: A questionnaire was distributed to institutions that perform solid organ transplantation in Japan, and clinical information was collected from patients who underwent transplantation between 2001 and 2010 and who exhibited de novo malignancies. RESULTS: Nine thousand two hundred ten solid organ transplants (kidney, 49.9%; liver, 45.9%; heart, 0.9%; lung, 1.2%; pancreas, 1.9%; small intestine, 0.2%) were performed. Four hundred seventy-nine (5.2%) cases of de novo malignancy were identified. The transplanted organs of the patients included the kidney (n = 479, 54.8%), liver (n = 186, 38.8%), heart (n = 5, 0.1%), lung (n = 18, 3.8%), pancreas (n = 9, 1.9%), and small intestine (n = 1, 0.02%). The most common malignancies were post-transplant lymphoproliferative disorder (n = 87) and cancers of the kidney (n = 43), stomach (n = 41), large intestine (n = 41), and lung (n = 36). CONCLUSIONS: This is the first national survey of the incidence of de novo malignancy in Japan. Further study is required to identify the risk of de novo malignancy in organ transplant recipients in comparison to the general population, namely the standardized incidence ratio.

Modeling preoperative risk factors for potentially lethal morbidities using a nationwide Japanese web-based database of patients undergoing distal gastrectomy for gastric cancer.

BACKGROUND: Most risk models for mortality and morbidity after distal gastrectomy have been created based on relatively small retrospective studies, and a model originating from nationwide database has been lacking. This study aimed to identify preoperative risk factors that predict the postoperative morbidities closely associated with mortality in gastric cancer patients undergoing distal gastrectomy, using data from the National Clinical Database (NCD), a nationwide web-based database in Japan. METHODS: We analyzed records from the NCD for 65,906 patients who underwent distal gastrectomy in 1,986 hospitals during 2011 and 2012. Using 80 % of these patients, we identified independent preoperative predictors for morbidities closely related with mortality. These risk factors were then validated using the remaining 20 % of patients from 2011 to 2012 and the further 35,575 records from 2013. RESULTS: Operative mortality was 1.07 % and overall morbidity was 14.2 % for the development data set. We selected eight morbidities that were closely associated with postoperative mortality, and then identified between 13 and 25 independent preoperative risk factors for each of the eight morbidities. Of these, old age, female gender, and poor ADL were the factors most frequently associated with the morbidities. The C-indices for each morbidity from the 2011 to 2012 validation data set were favorable as follows: unplanned intubation (0.797), pneumonia (0.784), systemic sepsis (0.748), renal failure (0.832), cardiac events (0.728), large blood transfusions (0.700), central nervous system (CNS) events (0.779), and anastomotic leakage (0.658). Similar C-indices were obtained for each mortality using the 2013 validation data set. CONCLUSIONS: In this study, we successfully constructed an acceptable risk model using preoperative risk factors to predict eight postoperative morbidities highly associated with mortality in gastric cancer patients. This risk model could help to tailor perioperative management and improve clinical outcomes for patients who undergo distal gastrectomy.

Development and external validation of preoperative risk models for operative morbidities after total gastrectomy using a Japanese web-based nationwide registry.

BACKGROUND: Total gastrectomy is a relatively difficult and invasive procedure among gastrointestinal surgeries, and major morbidities following total gastrectomy can be serious and fatal. This study aimed to develop and validate preoperative risk models of morbidities associated with total gastrectomy using a Japanese web-based nationwide registry. METHODS: The national clinical database was used to retrieve the records of 39,253 patients who underwent total gastrectomy in 1,841 hospitals between January 1, 2011 and December 31, 2012. RESULTS: Mean patient age was 69.1 years, and 73.8% of the patients were male. The overall morbidity rate was 21.5%, which included 8.1% with surgical site infection (SSI), 4.5% with anastomotic leak, 5.0% with pancreatic fistula, 3.7% with pneumonia, 1.9% with prolonged ventilation, and 1.2% with renal failure. Sex, splenectomy, and Brinkman index were selected as common risk factors for SSI, anastomotic leak, and pancreatic fistula. Pancreatectomy was the most significant preoperative risk factor in the risk model of SSI and pancreatic fistula. Need of assistance with activities of daily living, chronic obstructive pulmonary disease, previous cerebrovascular disease, American Society of Anesthesiologists score class 3 and over, presence of esophageal cancer, and body mass index more than 25 were selected as common risk factors for pneumonia, prolonged ventilation over 48 h, and renal failure. CONCLUSIONS: We have created the first reported risk models of morbidities associated with total gastrectomy, using a Japanese nationwide database. The risk models developed in this study may be useful to preoperatively predict operative morbidities in patients undergoing total gastrectomy.

Association between the participation of board-certified surgeons in gastroenterological surgery and operative mortality after eight gastroenterological procedures.

PURPOSE: The aim of this study is to evaluate the association between the participation of board-certified surgeons in gastroenterological surgery (BCS-Gs) and the surgical outcomes of gastroenterological surgery. METHODS: Data from the National Clinical Database on patients who underwent eight major gastroenterological procedures were analyzed retrospectively. First, the ratio of cases in which BCS-G were involved to the total cases was calculated for each procedure, and the impact of BCS-G involvement on surgical outcome was assessed by comparing mortality rates in the group with BCS-G involvement vs. the group without BCS-G involvement. Second, the differences in the observed/expected ratio were assessed among four hospital categories according to the available BCS-G number. Finally, the impact of the hospital BCS-G number on mortality was evaluated. RESULTS: The ratio of BCS-G involvement ranged from 59.0 % for acute diffuse peritonitis to 89.1 % for hepatectomy, and the mortality rate was significantly lower for three procedures when BCS-Gs participated as the operator or assistant. The observed/expected ratio of hospitals with four or more BCS-Gs was less than 1.0 for all the procedures assessed. A multivariable logistic regression model showed that the hospital BCS-G number was a predictor of operative mortality. CONCLUSIONS: BCS-Gs contribute to favorable outcomes of gastroenterological surgery in Japan. The hospital BCS-G number is a surrogate marker of operative mortality.

Lectin inhibits antigen-antibody reaction in a glycoform-specific manner: Application for detecting α2,6sialylated-carcinoembryonic antigen.

Carcinoembryonic antigen (CEA) is a glycoprotein marker, which is widely used for diagnosing various cancers, especially colon adenocarcinoma. In addition, CEA mediates homotypic adhesion of colon adenocarcinoma cells, which appears to favor hematogenous metastasis. CEA carries α2,6sialyl residues on its N-glycans whereas a normal counterpart, normal fecal antigen-2, does α2,3sialyl residues, suggesting that cancer-specific  α2,6sialylation on CEA may play a role for cell invasion and metastasis. A simple and rapid estimation of α2,6sialyled CEA in detergent extracts from formalin-fixed colon adenocarcinoma by "lectin inhibition" is reported. In the lectin inhibition method, Sambucus sieboldiana Agglutinin (SSA) lectin, an α2,6sialic acid binder, was used as a glycoform-specific inhibitor for antigen-antibody reaction in ELISA. Detergent extracts from colon adenocarcinoma showed a fair amount of ELISA signal in the absence of SSA whereas the signal was markedly reduced (45≈74%) in the presence of SSA, suggesting that the extracts contains α2,6sialyled CEA. The presence of α2,6sialyled CEA in the extracts was confirmed by lectin microarray, in which SSA, Sambucus nigra agglutinin, and Trichosanthes japonica agglutinin I lectins were used as α2,6sialyl binders. Thus lectin inhibition is a simple and rapid method for detecting α2,6sialyled CEA even in crude detergent extracts from formalin-fixed adenocarcinoma tissue.

M1 macrophage infiltrations and histological changes in the liver after portal vein embolization using fibrinogen and OK432 in the rat.

The mechanism of anti-tumor effect of transarterial Immuno-Embolization (TIE) using OK-432 has not been well elucidated. In this study, we aimed to investigate the tissue injury and immune response after portal venous embolization (PVE) with/without OK-432. Embolic materials (L group: lipiodol, LF group: lipiodol+fibrinogen, LO group: lipiodol+OK-432, LFO group: lipiodol+fibrinogen+OK-432) were administered via the right portal vein in Wistar rats. The histological findings in LFO group demonstrated liver damage with severe architectural changes. The concentrations of CD68(+) cells were observed in a time-dependent manner; it was significantly increased in the LO group on day 1 and in the LFO group on day 3. CD68(+)CD163(-) macrophages significantly increased in the LFO group on day 7 (P<0.05). In conclusion, PVE with fibrinogen and OK-432 markedly increased the CD68(+)CD163(-) infiltrating macrophages around the peri-portal area in the liver. This novel technique could be applied as immune-enhanced chemo-embolization of liver tumors.