Impact of technically qualified surgeons on laparoscopic colorectal resection outcomes: results of a propensity score-matching analysis.

BACKGROUND: The Endoscopic Surgical Skill Qualification System (ESSQS) was introduced in Japan to improve the quality of laparoscopic surgery. This cohort study investigated the short- and long-term postoperative outcomes of colorectal cancer laparoscopic procedures performed by or with qualified surgeons compared with outcomes for unqualified surgeons. METHODS: All laparoscopic colorectal resections performed from 2010 to 2013 in 11 Japanese hospitals were reviewed retrospectively. The procedures were categorized as performed by surgeons with or without the ESSQS qualification and patients' clinical, pathological and surgical features were used to match subgroups using propensity scoring. Outcome measures included postoperative and long-term results. RESULTS: Overall, 1428 procedures were analysed; 586 procedures were performed with ESSQS-qualified surgeons and 842 were done by ESSQS-unqualified surgeons. Upon matching, two cohorts of 426 patients were selected for comparison of short-term results. A prevalence of rectal resection (50·3 versus 40·5 per cent; P < 0·001) and shorter duration of surgery (230 versus 238 min; P = 0·045) was reported for the ESSQS group. Intraoperative and postoperative complication and reoperation rates were significantly lower in the ESSQS group than in the non-ESSQS group (1·2 versus 3·6 per cent, P = 0·014; 4·6 versus 7·5 per cent, P = 0·025; 1·9 versus 3·9 per cent, P = 0·023, respectively). These findings were confirmed after propensity score matching. Cox regression analysis found that non-attendance of ESSQS-qualified surgeons (hazard ratio 12·30, 95 per cent c.i. 1·28 to 119·10; P = 0·038) was independently associated with local recurrence in patients with stage II disease. CONCLUSION: Laparoscopic colorectal procedures performed with ESSQS-qualified surgeons showed improved postoperative results. Further studies are needed to investigate the impact of the qualification on long-term oncological outcomes.

ANTECEDENTES: El Sistema de Certificación de Habilidades Quirúrgicas Endoscópicas (Endoscopic Surgical Skill Qualification System, ESSQS) fue introducido en Japón para mejorar la calidad de la cirugía laparoscópica. En este estudio de cohortes se investigaron los resultados postoperatorios a corto y a largo plazo de las intervenciones laparoscópicas de cáncer colorrectal realizadas por o con la asistencia de cirujanos con certificación en comparación con cirujanos no certificados. MÉTODOS: Todas las resecciones colorrectales laparoscópicas realizadas entre 2010 y 2013 en 11 hospitales japoneses fueron revisadas retrospectivamente. Los procedimientos se clasificaron en función de si habían sido realizados por cirujanos con o sin certificación del ESSQS, y las características clínicas, patológicas y quirúrgicas de los pacientes se utilizaron para emparejar los subgrupos mediante puntuaciones de propensión. Las variables de resultado incluyeron los resultados postoperatorios y a largo plazo RESULTADOS: En total se analizaron 1.428 procedimientos, incluyendo 586 y 842 procedimientos realizados con y sin cirujanos certificados por ESSQS, respectivamente. Tras el emparejamiento, se seleccionaron dos cohortes de 426 pacientes para la comparación de resultados a corto plazo. Se observó una mayor prevalencia de resecciones rectales (50,3% versus 40,1%, P = 0,0001) y un tiempo quirúrgico más corto (230 versus 238 min, P = 0,04) en el grupo ESSQS. Las tasas de complicaciones intra- y postoperatorias y de reoperaciones fueron significativamente más bajas en el grupo ESSQS que en el grupo no ESSQS (1,2%, 4,6% y 1,9% versus 3,6%, 7,5% y 3,9%, P = 0,01; 0,03, y 0,02, respectivamente). Estos hallazgos se confirmaron tras el análisis de emparejamiento por puntaje de propensión. El análisis de regresión de Cox mostró que la no participación de cirujanos certificados con ESSQS (razón de oportunidades, odds ratio, OR 12,3; i.c. del 95%, 1,28-119,1; P = 0,03) se asoció independientemente con la recidiva local en los casos en estadio II. CONCLUSIÓN: Los procedimientos colorrectales laparoscópicos realizados por cirujanos certificados por ESSQS presentaron mejores resultados postoperatorios. Son necesarios más estudios para determinar el impacto de la certificación en los resultados oncológicos a largo plazo.

Transition and post-transition metal ions in borate glasses: Borate ligand speciation, cluster formation, and their effect on glass transition and mechanical properties.

A series of transition and post-transition metal ion (Mn, Cu, Zn, Pb, Bi) binary borate glasses was studied with special consideration of the cations impact on the borate structure, the cations cross-linking capacity, and more generally, structure-property correlations. Infrared (IR) and Raman spectroscopies were used for the structural characterization. These complementary techniques are sensitive to the short-range order as in the differentiation of tetrahedral and trigonal borate units or regarding the number of non-bridging oxygen ions per unit. Moreover, vibrational spectroscopy is also sensitive to the intermediate-range order and to the presence of superstructural units, such as rings and chains, or the combination of rings. In order to clarify band assignments for the various borate entities, examples are given from pure vitreous B2O3 to meta-, pyro-, ortho-, and even overmodified borate glass compositions. For binary metaborate glasses, the impact of the modifier cation on the borate speciation is shown. High field strength cations such as Zn2+ enhance the disproportionation of metaborate to polyborate and pyroborate units. Pb2+ and Bi3+ induce cluster formation, resulting in PbOn- and BiOn-pseudophases. Both lead and bismuth borate glasses show also a tendency to stabilize very large superstructural units in the form of diborate polyanions. Far-IR spectra reflect on the bonding states of modifier cations in glasses. The frequency of the measured cation-site vibration band was used to obtain the average force constant for the metal-oxygen bonding, FM-O. A linear correlation between glass transition temperature (Tg) and FM-O was shown for the metaborate glass series. The mechanical properties of the glasses also correlate with the force constant FM-O, though for cations of similar force constant the fraction of tetrahedral borate units (N4) strongly affects the thermal and mechanical properties. For paramagnetic Cu- and Mn-borate glasses, N4 was determined from the IR spectra after deducing the relative absorption coefficient of boron tetrahedral versus boron trigonal units, α = α4/α3, using NMR literature data of the diamagnetic glasses.

Hepatic arterial infusion chemotherapy with cisplatin before radical local treatment of early hepatocellular carcinoma (JIS score 0/1) improves survival.

BACKGROUND: It has not yet been determined whether hepatic arterial infusion (HAI) chemotherapy improves survival in patients with early hepatocellular carcinoma (HCC). We evaluated the effectiveness of HAI with high-concentration cisplatin (DDP-H) for the treatment of HCC by comparing outcomes between patients who received HAI with DDP-H before radical local treatment of early-stage HCC [Japan Integrated Staging (JIS) score 0/1] and patients who did not receive HAI chemotherapy. PATIENTS AND METHODS: Survival was analyzed in 114 patients with early-stage HCC who underwent radical local treatment. The patients were divided into two groups: a HAI group (n = 79) who received DDP-H infusion into the whole liver via the proper hepatic artery, and a non-HAI group (n = 35) who did not receive HAI chemotherapy. RESULTS: The cumulative survival rates at 1, 3, and 5 years were 77.4%, 69.2%, and 55.3% in the non-HAI group and 97.4%, 87.0%, and 84.4% in the HAI group, respectively. Survival time prolonged significantly in the HAI group compared with the non-HAI group (log-rank test: P = 0.023; generalized Wilcoxon test: P = 0.012) Multivariate analysis using the Cox proportional hazards model identified HAI with DDP-H as the most important factor affecting survival. CONCLUSIONS: Whole-liver HAI with DDP-H before radical local treatment can improve the prognosis of patients with early-stage HCC.

Status of a compact electron cyclotron resonance ion source for National Institute of Radiological Sciences-930 cyclotron.

The Kei-source is a compact electron cyclotron resonance ion source using only permanent magnets and a frequency of 10 GHz. It was developed at the National Institute of Radiological Sciences (NIRS) for producing C(4+) ions oriented for high-energy carbon therapy. It has also been used as an ion source for the NIRS-930 cyclotron. Its microwave band region for the traveling-wave-tube amplifier and maximum output power are 8-10 GHz and 350 W, respectively. Since 2006, it has provided various ion beams such as proton, deuteron, carbon, oxygen, and neon with sufficient intensity (200 µA for proton and deuteron, 50 µA for C(4+), for example) and good stability for radioisotope production, tests of radiation damage, and basic research experiments. Its horizontal and vertical emittances were measured using a screen monitor and waist-scan. The present paper reports the current status of the Kei-source.

Increased systemic inflammatory interleukin-1ß and interleukin-6 during agitation as predictors of Alzheimer's disease.

OBJECTS: Identification of biomarkers for Alzheimer's disease (AD) is important for its early diagnosis and prevention and a key in advancing our understanding of its pathophysiology. The aim of this study was to determine whether systemic inflammatory interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) as well as hypertension (HT), diabetes mellitus (DM), and body mass index (BMI) are predictors of AD. METHODS: We performed a 10-year follow-up study on 133 elderly who were institutionalized in a nursing home. The associations of IL-1ß and IL-6 at both rest and agitation, as well as HT, DM, and BMI at baseline, were analyzed with the incidences of vascular dementia (VD) and AD during a 10-year follow-up period. RESULTS: The Kaplan-Meier method with log-rank test and Cox regression analyses for the total of 133 subjects showed significantly higher incidences of both VD and AD in subjects with DM or HT at baseline. Resting IL-1ß or IL-6 value, or agitation score, was not significantly associated with the subsequent development of VD or AD. The analyses of 40 subjects who had shown agitation at least once in the previous 3 months demonstrated that IL-1ß and IL-6 values at the agitation stage were significantly associated with AD, but not with VD. CONCLUSION: Our results indicate that systemic inflammatory IL-1ß and IL-6 at the agitation stage are risk factors for the development of AD, but not VD. Inflammatory mechanisms for AD seem to be causal and specific to the development of AD.

Status of ion sources at National Institute of Radiological Sciences.

The National Institute of Radiological Sciences (NIRS) maintains various ion accelerators in order to study the effects of radiation of the human body and medical uses of radiation. Two electrostatic tandem accelerators and three cyclotrons delivered by commercial companies have offered various life science tools; these include proton-induced x-ray emission analysis (PIXE), micro beam irradiation, neutron exposure, and radioisotope tracers and probes. A duoplasmatron, a multicusp ion source, a penning ion source (PIG), and an electron cyclotron resonance ion source (ECRIS) are in operation for these purposes. The Heavy-Ion Medical Accelerator in Chiba (HIMAC) is an accelerator complex for heavy-ion radiotherapy, fully developed by NIRS. HIMAC is utilized not only for daily treatment with the carbon beam but also for fundamental experiments. Several ECRISs and a PIG at HIMAC satisfy various research and clinical requirements.

Physics research and technology developments of electron string ion sources.

The most recent experimental information on electron string phenomenon, such as two step transition to electron string state, stability of e-strings in condition of electron energy recuperation, are described. The new technology developments of electron string ion sources (ESIS) include pulse injection of gaseous species in e-string and its efficient conversion to ion beams, slow ion extraction, ion-ion cooling of heavy ions with CH(4) coolant, and a progress in the construction of the new Joint Institute for Nuclear Research ESIS with 6 T solenoid are briefly considered.

Association between altered systemic inflammatory interleukin-1beta and natural killer cell activity and subsequently agitation in patients with Alzheimer disease.

OBJECTIVE: Alzheimer's disease (AD) is a neurodegenerative disorder that is the most common cause of dementia in the elderly and is frequently accompanied by emotional disorder, including agitation. Although evidence of neuroendocrine immune and inflammatory functions during emotional changes has been accumulated, the pathogenic mechanisms in the development of agitation accompanied by AD remain to be elucidated. METHODS: To clarify the involvement of neuroendocrine and immune and inflammatory systems in agitation in AD, we examined agitation levels, circadian rhythms of behavior, cortisol, interleukin-1beta (IL-1beta), and natural killer cell activity (NKCA) in controls without dementia and 16 AD patients who were recognized to be easily agitated in their nursing homes. These behavioral and blood indicators were assessed according to the progress of the stage of agitation in 16 AD patients (stable, pre-agitation, and agitation stages). RESULTS: Elevations in night behavior and blood cortisol, IL-1beta and an reduced blood NKCA level in the evening were observed not only in the agitation stage, but also when stable in AD patients as compared to the control. Increased IL-1beta and decreased NKCA occurred in both the morning and evening in pre-agitation and agitation stages in AD. CONCLUSIONS: The increased IL-1beta and decreased NKCA with the progress of agitation in AD suggest that inflammation produces agitation and aggravates AD.

Micro-CT analysis of alveolar bone healing using a rat experimental model of critical-size defects.

OBJECTIVE: This study was designed to establish a rat model of a critical size alveolar bone defect. MATERIALS AND METHODS: Standardized buccal or mesiobuccal alveolar bone defects were made around the right first mandibular molar of 12-week-old rats, and the left was used as a control. Alveolar bone healing was examined quantitatively by three-dimensional micro-computed tomographic imaging. Bone matrix production of osteoblasts and osteocytes during repair of alveolar bone defects was examined with in situ hybridization for type I collagen. RESULTS: Buccal defects were repaired significantly and the volume decreased by 88.3% in week 24, whereas mesiobuccal defects were repaired little. Osteoblasts and osteocytes expressed type I collagen in both defects in week 3 but showed little expression by week 6 and thereafter, leaving the mesiobuccal defects largely unrepaired. CONCLUSION: The mesiobuccal defect is a critical-size defect that is not ultimately repaired with bone. It may be an appropriate experimental model for investigating the effectiveness of bone regenerative agents in human alveolar bone loss.

Bone formation in rat calvaria ceases within a limited period regardless of completion of defect repair.

A bone defect that is not repaired with bone completely is designated a non-union defect or a critical-size defect. The biological mechanism that regulates the process of bone repair of the critical-size defect remains unknown. The present study was designed to investigate bone repair in a critical-size defect compared with that in a smaller or non-critical-size defect. Our original standardized rat calvarial bone defect model was used for the experiment. The rate of bone formation was examined with X-ray morphometry and the bone production of osteoblasts and osteocytes was assessed by molecular histology with in situ hybridization for type I collagen and osteocalcin. Formation of repaired bone ceased within 24 weeks in both critical- and non-critical-size defects i.e. regardless of completion of the defect repair. The results suggested that osteoblasts and osteocytes cease bone formation, and the differentiation of osteoblast progenitors declines in 24 weeks. Also, bone repair proceeds from the periosteum on both sides of the parietal bone but not from the surface of the bony edge around the original defect. The results could provide useful information for clinical research on bone repair.

Root development of rat tooth germs implanted in the tooth socket and in the subcutaneous tissue.

OBJECTIVE: This study was designed to investigate root development of a rat tooth germ implanted in a tooth socket or in a subcutaneous region. MATERIALS AND METHODS: Tooth germs of the upper left first molars in 2-week-old rats were extracted and implanted in the original tooth socket or in the subcutaneous region of the back. The upper right first molar was used as a control. The rats were fixed in weeks 1, 2, 4, 8 and 12. The root development was examined quantitatively with X-ray radiographic morphometry. The cellular activity of producing matrix proteins was assessed using in situ hybridization for type I collagen. RESULTS: Root development was observed in the implanted teeth in the tooth socket as also in the control teeth. In contrast, roots hardly developed in subcutaneously implanted teeth. Histology showed that periodontal ligaments were arranged around roots of implanted teeth in the tooth socket as around control teeth, but few periodontal ligaments were identified in the subcutaneous implantation. Dentin and cementum formed in both the implanted teeth as also in the control teeth and odontoblasts, cementoblasts and cementocytes expressed type I collagen. CONCLUSION: Tooth sockets may possess specific environments that allow root development of a tooth germ.

Electronic polarizability and Judd-Ofelt parameters of Nd3+ and Er3+ ions in transparent crystallized glasses with nonlinear optical Ba2 TiSi2O8 nanocrystals.

Transparent crystallized glasses consisting of nonlinear optical Ba(2)TiSi(2)O(8) nanocrystals are prepared in Eu(2)O(3)-, Nd(2)O(3)-, and Er(2)O(3)-doped 40BaO-20TiO(2)-40SiO(2) glasses by a conventional heat treatment method in order to clarify the optical properties of rare-earth (RE) ions in nanocrystals. The electronic polarizabilities of crystallized glasses are evaluated from the values of density and refractive index, and are found to decrease due to nanocrystallization, which indicates that the chemical bonding state in the crystallized glasses is more covalent compared to the precursor glasses. It is proposed from x-ray diffraction analyses and photoluminescence spectra of Eu(3+) ions that RE ions such as Nd(3+) and Eu(3+) are incorporated into Ba(2)TiSi(2)O(8) nanocrystals. The Judd-Ofelt parameters, Omega(t) (t=2, 4, and 6), of Nd(3+) and Er(3+) ions are evaluated from optical absorption spectra. It is observed that the Omega(2) parameter of Nd(3+) and Er(3+) increases largely due to nanocrystallization, suggesting that the site symmetry of Nd(3+) and Er(3+) ions in nanocrystallized glasses is largely distorted due to their incorporations into the Ba(2+) sites in Ba(2)TiSi(2)O(8) nanocrystals. The change in the Omega(4) and Omega(6) parameters due to nanocrystallization is small. It is proposed that nonlinear optical Ba(2)TiSi(2)O(8) nanocrystals including RE ions would have a high potential as active optical materials.

Development of gas pulsing system for electron cyclotron resonance ion source.

A gas-pulsing system for an electron cyclotron resonance ion source with all permanent magnets (Kei2 source) at NIRS has been developed and tested. The system consists of a small vessel (30 ml) to reserve CH(4) gas and two fast solenoid valves that are installed at both sides of the vessel. They are connected to each other and to the Kei2 source by using a stainless-steel pipe (4 mm inner diameter), where the length of the pipe from the valve to the source is 60 cm and the conductance is 1.2 l/s. From the results of the test, almost 300 e microA for a pulsed (12)C(4+) beam was obtained at a Faraday cup in an extraction-beam channel with a pressure range of 4000 Pa in the vessel. At this time, the valve has an open time of 10 ms and the delay time between the valve open time and the application of microwave power is 100 ms. In experiments, the conversion efficiency for input CH(4) molecules to the quantity of extracted (12)C(4+) ions in one beam pulse was found to be around 3% and the ratio of the total amount of the gas requirement was only 10% compared with the case of continuous gas provided in 3.3 s of repetition in HIMAC.

Atom probe specimen fabrication methods using a dual FIB/SEM.

A dual FIB/SEM provides solutions to many challenges in atom probe specimen preparation. When combined with an in situ lift-out capability, the versatility of this tool allows almost any region of interest, in almost any geometry, to be placed at the apex of a specimen tip. Several preparation techniques have been developed in response to specific application requirements; for example, in cases where materials are not suitable for electropolishing, or where site-specific analysis is required. Two general techniques, with wide-ranging potential applications, are described in detail here. The first is a 'cut-out' technique that provides a relatively quick means of micro-tip specimen preparation from bulk material samples. The second method is a 'lift-out' technique that can be used in an in situ or ex situ mode and does not require the preparation of pre-sharpened mounting points.

Intravenous infusion of immortalized human mesenchymal stem cells protects against injury in a cerebral ischemia model in adult rat.

Intravenous infusion of bone marrow cells has demonstrated therapeutic efficacy in animal models of cerebral ischemia and spinal cord injury. We intravenously delivered human mesenchymal stem cells (SH2+, SH3+, CD34-, and CD45-) immortalized with a human-telomerase gene (hTERT-MSCs) and transfected with eGFP or LacZ into rats 12 h after induction of transient middle cerebral artery occlusion (MCAO), to study their potential therapeutic benefit. hTERT-MSCs were delivered at 12 h after lesion induction. Lesion size was assessed using MR imaging and spectroscopy, and histological methods. Functional outcome was assessed using the Morris water maze and a treadmill test. Intravenous delivery of hTERT-MSCs reduced lesion volume and the magnitude of the reduction and functional improvement was positively correlated with the number of cells injected. The reduction of lesion size could be assessed in vivo with MRI and MRS and was correlated with subsequent histological examination of the brain. This work demonstrates that highly purified hTERT-MSCs reduce cerebral infarction volume and improve functional outcome.

Overexpression of anti-apoptotic Mcl-1 in testicular germ cell tumours.

AIMS: To determine the expression of Mcl-1 in testicular germ cell tumours in order to clarify the role of this anti-apoptotic factor in these tumours. Various members of the Bcl-2 family have been implicated in the apoptotic mechanisms regulating germ cell apoptosis. Mcl-1 is an anti-apoptotic Bcl-2 family member and has recently been reported to be related to the progression of malignancy; however, the involvement of Mcl-1 in the development of germ cell tumours is still unknown. METHODS AND RESULTS: Mcl-1 expression in testicular germ cell tumours was investigated by immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR). By immunohistochemistry, overexpression of Mcl-1 was present in all germ cell tumours that were studied, including embryonal carcinoma and yolk sac tumour, as well as choriocarcinoma and teratoma. In teratomas, Mcl-1 was widely distributed in the epithelial, myogenic, neural and mesenchymal components. RT-PCR analysis after microdissection revealed high levels of Mcl-1 mRNA in all tumour variants compared with non-neoplastic germ cells. CONCLUSION: Overexpression of anti-apoptotic Mcl-1 may function to enhance the viability of testicular germ cells, thereby leading to tumorigenesis.

Association between K469E allele of intercellular adhesion molecule 1 gene and inflammatory bowel disease in a Japanese population.

BACKGROUND AND AIMS: The genetic contribution to inflammatory bowel disease (IBD) is under investigation. Recent evidence indicates a significant linkage between a locus on chromosome 19p13 and IBD. We investigated the association between an intercellular adhesion molecule 1 gene (ICAM-1) polymorphism located on chromosome 19p13 and IBD in a Japanese population. METHODS: We compared 207 Japanese patients who had IBD (79 with Crohn's disease (CD); 128 with ulcerative colitis (UC)) with 103 unrelated Japanese controls. We determined R241G and K469E polymorphisms of the ICAM-1 gene using polymerase chain reaction (PCR) techniques. RESULTS: Both frequency and carriage rate of the K469 allele were significantly higher in IBD patients than in controls (allelic frequency, p(c)=0.0026; carriage rate, p(c)=0.0034; odds ratio 2.59; 95% confidence interval 1.42-4.68). Furthermore, the frequency of the K469 allele was significantly increased in both CD and UC. Subgroup analysis demonstrated that both K469 allelic frequency and K469 carriage rate were significantly higher in patients with the small bowel and colon type of CD and entire colitis compared with healthy controls. CONCLUSIONS: We identified an overall association between IBD and ICAM-1 K469 in a Japanese population. Further studies of this chromosome region are required to elucidate the gene responsible for IBD.

Superficial depressed-type cancer monitored by colonoscopy through the early phase of invasion.

Although previous retrospective reports have demonstrated the developmental course of several colorectal tumors, the natural history and progression of depressed carcinoma, especially in the early stage, remains obscure. We report a case of superficial depressed tumor in the transverse colon in a 71-year-old man, which did not change in size and gross configuration through prospective colonoscopic observation over a period of 19 months but which was finally diagnosed as early-stage submucosal invasive cancer. Most depressed cancers have been supposed to arise de novo and grow rapidly, showing aggressive behavior when 10 mm or less in size. However, this case report may suggest that even a depressed tumor may grow to approximately 10 mm within the mucosal layer over a few years and that the growth of colorectal tumors, whether they are polypoid or depressed in configuration, might be fairly slow.

Correlation between serum phospholipase A(2) IIA levels and histological activity in patients with ulcerative colitis.

BACKGROUND AND AIMS: Phospholipase A(2) (PLA(2)) participates in the regulation of phospholipid metabolism and biosynthesis of eicosanoids, serum levels of PLA(2) are suggested to reflect the disease activity in patients with ulcerative colitis (UC). We examined the relationship between histological disease activity and serum levels of PLA(2) IIA and also clarified mucosal production sites of PLA(2) IIA by immunohistochemistry. PATIENTS AND METHODS: Serum samples from 44 patients with UC, 125 with Crohn's diseases (CD), and 68 controls were studied. Biopsy specimens of colonic mucosa obtained from 23 patients with UC were used for assessment of histological activity. The histological score was determined active (1) or inactive (0), and the sum of each histological score from ten segments of the large intestine was assessed as disease activity. The levels of PLA(2) IIA in sera were measured by a radioimmunoassay kit using a specific monoclonal antibody; immunohistochemical study was performed using the same monoclonal antibody. RESULTS: The serum PLA(2) IIA levels in patients with UC and CD were significantly higher than those of controls. Serum PLA(2) IIA levels in UC were closely correlated with histological disease activity. Immunohistochemical study showed the production of PLA(2) IIA by the polymorphonuclear cells, macrophages, and colonic epithelial cells. CONCLUSION: Serum PLA(2) IIA is a good candidate for assessing disease activity in UC as one of clinical laboratory tests.

Bcl-2 expression and frequency of apoptosis correlate with morphogenesis of colorectal neoplasia.

AIM: To investigate whether the expression of apoptosis and cell proliferation related proteins is related to the macroscopic form of colorectal neoplasia. METHODS: The extent of apoptosis, using the 3' end DNA labelling method, and the immunohistochemical expression of cell proliferation (Ki-67) and apoptosis related proteins (Bcl-2, Bak, and p53) were investigated in 64 colorectal adenomas and 22 early carcinomas extending no further than the upper submucosal region. The specimens were classified into three types of macroscopic form (polypoid, flat, and depressed). RESULTS: The Ki-67 labelling index and the Bak score did not differ significantly among each macroscopic form. In contrast, the apoptotic index and the Bcl-2 score changed significantly according to the macroscopic forms. Compared with polypoid and flat tumours, depressed tumours had a significantly lower apoptotic index (2.84, 2.28, and 1.44, respectively) and a significantly lower Bcl-2 score (3.18, 2.70, and 1.64, respectively). The proliferation/apoptosis ratio was significantly lower in polypoid tumours than in the other two macroscopic forms. The Bcl-2 score became significantly lower as the tumours flattened or took on a depressed form. Immunohistochemical p53 overexpression did not correlate with the macroscopic forms. CONCLUSIONS: These results suggest that differences in both Bcl-2 expression and apoptosis may play an important role in the morphogenesis of colorectal neoplasia.