Respiratory motion tracking of spine stereotactic radiotherapy in prone position.

PURPOSE: The CyberKnife system is a specialized device for non-coplanar irradiation; however, it possesses the geometric restriction that the beam cannot be irradiated from under the treatment couch. Prone positioning is expected to reduce the dose to normal lung tissue in spinal stereotactic body radiotherapy (SBRT) owing to the efficiency of beam arrangement; however, respiratory motion occurs. Therefore, the Xsight spine prone tracking (XSPT) system is used to reduce the effects of respiratory motion. The purpose of this study was to evaluate the motion-tracking error of the spine in the prone position. MATERIALS AND METHODS: Data from all 25 patients who underwent spinal SBRT at our institution between April 2020 and February 2022 using CyberKnife (VSI, version 11.1.0) with the XSPT tracking system were retrospectively analyzed using log files. The tumor motion, correlation, and prediction errors for each patient were examined. Furthermore, to assess the potential relationships between the parameters, the relationships between the tumor-motion amplitudes and correlation or prediction errors were investigated using linear regression. RESULTS: The tumor-motion amplitudes in each direction were as follows: superior-inferior (SI), 0.51 ± 0.39 mm; left-right (LR), 0.37 ± 0.29 mm; and anterior-posterior (AP), 3.43 ± 1.63 mm. The overall mean correlation and prediction errors were 0.66 ± 0.48 mm and 0.06 ± 0.07 mm, respectively. The prediction errors were strongly correlated with the tumor-motion amplitudes, whereas the correlation errors were not. CONCLUSIONS: This study demonstrated that the correlation error of spinal SBRT in the prone position is sufficiently small to be independent of the tumor-motion amplitude. Furthermore, the prediction error is small, contributing only slightly to the tracking error. These findings will improve the understanding of how to compensate for respiratory-motion uncertainty in the prone position.

Efficacy and safety of pararectus approach for the treatment of acetabular fractures: A systematic review and meta-analysis.

BACKGROUND: The pararectus (PR) approach combines the advantages of the second window of the ilioinguinal approach and the medial view of the modified Stoppa approach. However, it is unclear whether the PR approach is more effective or safer than the other approaches, as few clinical studies have compared the PR approach with the other approaches. The aim of this study was to provide a systematic review and meta-analysis comparing the PR approach with the other approaches for the treatment of acetabular fractures and to answer the following question: Are the results of the PR approach superior to those of the other approaches in terms of reduction quality, operative time, operative blood loss, complications, and clinical outcomes for treatment of acetabular fractures? PATIENTS AND METHODS: A systematic literature review was conducted using relevant original studies from various databases. Pooling of data was performed using RevMan software (version 5.3, Cochrane Collaboration, Oxford, UK). A p-value<0.05 was considered to be significant. We calculated the mean differences for continuous data and odds ratio for dichotomous data with 95% confidence intervals for each outcome. Statistical heterogeneity was assessed based on I2 using the standard χ2 test. RESULTS: Five studies were included in this meta-analysis. The findings demonstrated that operative blood loss was significantly lower in the PR approach than in the other approaches (p=0.04). There was no significant difference in the rate of anatomical reduction, the operative time, the rate of complications, and the rate of excellent or good clinical score between the PR approach and the other approaches. DISCUSSION: The PR approach provided lower operative blood loss, although there was no significant difference in reduction quality, operative time, complications, and excellent or good clinical score between the PR approach and the other approaches. LEVEL OF EVIDENCE: III.

Case of a Deep Neck Abscess During Treatment for COVID-19.

BACKGROUND COVID-19 is treated using antiviral and immunosuppressive drugs. Therefore, patients treated for COVID-19 may have an increased risk of secondary infection and a masked inflammatory response. We present a case of a deep neck abscess caused by pyogenic sternoclavicular arthritis during treatment for COVID-19. CASE REPORT A 55-year-old man with COVID-19 was admitted to the hospital with hypoxemia. He was then treated with remdesivir, tocilizumab, and dexamethasone and was placed in the prone position. When his condition stabilized, pain in the left shoulder appeared. There was no fever or elevation in inflammation markers, and he was administered analgesics. However, the pain worsened and redness of the left neck appeared. Plain computed tomography (CT) showed swelling of the left neck muscles. Because cellulitis was suspected, he was treated with antibiotics, but his symptoms did not improve. Three days after the plain CT, contrast-enhanced CT showed sternoclavicular arthritis, deep neck abscess, and mediastinal abscess. Therefore, an emergency incisional drainage was performed under general anesthesia. Wound cleaning and drainage were continued after surgery, and after drainage tubes were removed, the patient was discharged on postoperative day 17. CONCLUSIONS Cervical infections after COVID-19 treatment have been reported in a few cases. Particularly, deep neck abscesses require more attention since they could be fatal if not treated immediately. If a secondary infection is suspected in a patient treated with immunosuppressive drugs for COVID-19, a thorough physical examination should be performed to avoid misdiagnosis.

Fiducial marker position affects target volume in stereotactic lung irradiation.

PURPOSE: Real-time tracking systems of moving respiratory targets such as CyberKnife, Radixact, or Vero4DRT are an advanced robotic radiotherapy device used to deliver stereotactic body radiotherapy (SBRT). The internal target volume (ITV) of lung tumors is assessed through a fiducial marker fusion using four-dimensional computed tomography (CT). It is important to minimize the ITV to protect normal lung tissue from exposure to radiation and the associated side effects post SBRT. However, the ITV may alter if there is a change in the position of the fiducial marker with respect to the tumor. This study investigated the relationship between fiducial marker position and the ITV in order to prevent radiation exposure of normal lung tissue, and correct target coverage. MATERIALS AND METHODS: This study retrospectively reviewed 230 lung cancer patients who received a fiducial marker for SBRT between April 2015 and September 2021. The distance of the fiducial marker to the gross tumor volume (GTV) in the expiratory (dex ) and inspiratory (din ) CT, and the ratio of the ITV/V(GTVex ), were investigated. RESULTS: Upon comparing each lobe, although there was no significant difference in the ddiff and the ITV/V(GTVex ) between all lobes for dex  < 10 mm, there was significant difference in the ddiff and the ITV/V(GTVex ) between the lower and upper lobes for dex ≥ 10 mm (p < 0.05). Moreover, there was significant difference in the ddiff and the ITV/V(GTVex ) between dex ≥10 mm and dex  < 10 mm in all lung regions (p < 0.05). CONCLUSION: The ITV that had no margin from GTVs increased when dex was ≥10 mm for all lung regions (p < 0.05). Furthermore, the increase in ITV tended to be greater in the lower lung lobe. These findings can help decrease the possibility of adverse events post SBRT, and correct target coverage.

Reactive oxygen species-inducing titanium peroxide nanoparticles as promising radiosensitizers for eliminating pancreatic cancer stem cells.

BACKGROUND: Despite recent advances in radiotherapy, radioresistance in patients with pancreatic cancer remains a crucial dilemma for clinical treatment. Cancer stem cells (CSCs) represent a major factor in radioresistance. Developing a potent radiosensitizer may be a novel candidate for the eradication of pancreatic CSCs. METHODS: CSCs were isolated from MIA PaCa-2 and PANC1 human pancreatic cancer cell lines. Titanium peroxide nanoparticles (TiOxNPs) were synthesized from titanium dioxide nanoparticles (TiO2NPs) and utilized as radiosensitizers when added one hour prior to radiation exposure. The antitumor activity of this novel therapeutic strategy was evaluated against well-established pancreatic CSCs model both in vitro and in vivo. RESULTS: It is shown that TiOxNPs combined with ionizing radiation exhibit anti-cancer effects on radioresistant CSCs both in vitro and in vivo. TiOxNPs exhibited a synergistic effect with radiation on pancreatic CSC-enriched spheres by downregulating self-renewal regulatory factors and CSC surface markers. Moreover, combined treatment suppressed epithelial-mesenchymal transition, migration, and invasion properties in primary and aggressive pancreatic cancer cells by reducing the expression of proteins relevant to these processes. Notably, radiosensitizing TiOxNPs suppressed the growth of pancreatic xenografts following primary or dissociating sphere MIA PaCa-2 cell implantation. It is inferred that synergy is formed by generating intolerable levels of reactive oxygen species (ROS) and inactivating the AKT signaling pathway. CONCLUSIONS: Our data suggested the use of TiOxNPs in combination with radiation may be considered an attractive therapeutic strategy to eliminate pancreatic CSCs.

Predicting factors of symptomatic radiation pneumonitis induced by durvalumab following concurrent chemoradiotherapy in locally advanced non-small cell lung cancer.

BACKGROUND: Concurrent chemoradiotherapy (CCRT) followed by durvalumab is the standard of care for unresectable locally-advanced non-small cell carcinoma (LA-NSCLC). However, a major concern about administration of durvalumab after CCRT is whether the incidence of symptomatic radiation pneumonitis (RP) may increase or not. In the present analysis, we report the initial results of CCRT followed by durvalumab in patients with LA-NSCLC in a real-world setting with focus on predicting factors for symptomatic RP. METHODS: Patients who were pathologically diagnosed as NSCLC and initiated treatment with CCRT followed by durvalumab between July 2018 to December 2019 were eligible for this study. Patients were included if they completed the planned CRT course and administered at least one course of durvalumab. We retrospectively investigated the preliminary survival outcome and incidence and predicting factors for symptomatic RP. RESULTS: Of the 67 patients who planned CCRT, 63 patients completed the entire CCRT course. Of these, 56 patients proceeded to consolidation with durvalumab. The median time to eternal discontinuation of durvalumab was 9.7 months. The cumulative proportion of the patients who exhibited symptomatic RP was 30, 40 and 44% at 3, 6 and 12 months, respectively. In multivariate analyses, pulmonary fibrosis score and lung V40 were significant predictive factors for symptomatic RP (p < 0.001, HR: 7.83, 95% CI: 3.38-18.13, and p = 0.034, HR: 3.17, 95% CI: 1.09-9.19, respectively). CONCLUSIONS: Pulmonary fibrosis sore and lung V40 were significant predictive factors for symptomatic RP. We should be cautious about the administration of durvalumab for patients having subclinical pulmonary fibrosis. To our best knowledge, this is one of the first report showing the predictive value of high dose volumes to the lung in patients with LA-NSCLC who received CCRT followed by durvalumab.

Efficacy of Spacers in Radiation Therapy for Locally Advanced Pancreatic Cancer: A Planning Study.

BACKGROUND/AIM: We aimed to investigate the dosimetric effects of a spacer placed between the pancreas and surrounding gastrointestinal structures in intensity-modulated radiation therapy (IMRT) planning to provide more effective radiation therapy for locally advanced pancreatic cancer (LAPC). PATIENTS AND METHODS: Treatment planning was performed for six patients with LAPC based on computed tomography images without spacers and with 5-mm or 10-mm spacers virtually inserted under the supervision of a hepatobiliary pancreatic surgeon. The prescription dose was 63 Gy in 28 fractions. RESULTS: With the exception of one case of pancreatic head cancer, planning target volume receiving ≥95% of the prescribed dose (PTV V95) was achieved by 90% or more by inserting a spacer, and by 95% or more in all 3 cases of pancreatic body and tail cancer by inserting a 10-mm spacer. CONCLUSION: IMRT with appropriate spacer placement may help provide high-dose treatment for LAPC and improve associated patient outcomes.

Oncogenic miRNAs Identified in Tear Exosomes From Metastatic Breast Cancer Patients.

BACKGROUND/AIM: Exosomes are produced by normal and cancer cells. Exosomes are found in the serum of cancer patients and have been used for diagnosis and prognosis. Recently tears from non-cancer patients have been found to contain exosomes. In the present report we describe tears from advanced breast-cancer patients. MATERIALS AND METHODS: We found oncogenic miRNAs in the exosomes isolated from tear fluids obtained from five patients with metastatic breast cancer and compared them with tear exosomes form eight healthy volunteers. RESULTS: Tear exosomes had a significantly higher quantity of exosome markers than serum exosomes (CD9, CD63). Tear exosomes were subjected to quantitative reverse-transcription polymerase reaction (qRT-PCR), and western blot analysis to elucidate the status of miRNAs, previously reported in serum from patients with metastatic breast cancer. qRT-PCR and western-blot analysis revealed that breast-cancer-specific miR-21 and miR-200c were highly expressed in tear exosomes from metastatic breast cancer patients in contrast to tear exosomes from healthy volunteers. CONCLUSION: Tear exosomes can be a potential source of diagnostic and prognostic biomarkers for metastatic breast cancer, and possibly other cancers or diseases.

National survey on total-body irradiation prior to reduced-intensity stem cell transplantation in Japan: The Japanese Radiation Oncology Study Group.

Reduced-intensity stem cell transplantation (RIST) minimizes the adverse effects of traditional hematopoietic stem cell transplantation, and low-dose total-body irradiation (TBI) is administered over a short period prior to RIST (TBI-RIST). Different institutes adopt different approaches for the administration of TBI-RIST, and since no study had previously investigated this issue, a survey of the TBI schedules in Japan was conducted. In October 2015, the Japanese Radiation Oncology Study Group initiated a national survey of TBI-RIST procedures conducted between 2010 and 2014. Of 186 institutions performing TBI, 90 (48%) responded to the survey, 78 of which performed TBI-RIST. Of 2488 patients who underwent TBI for malignant disease at these institutions, 1412 (56.8%) patients were treated for leukemia, 477 (19.2%) for malignant lymphoma, 453 (18.2) for myelodysplastic syndrome, 44 (1.8%) for multiple myeloma, and 102 (4.1%) for other malignant diseases. Further, 206 (52.0%) of 396 patients (a high proportion of patients) who underwent TBI for benign disease had aplastic anemia. The TBI-RIST equipment and treatment methods were similar to those used for myeloablative regimens. Routinely shielded organs included the lungs (43.6%), eyes (50.0%) and kidneys (10.2%). The ovaries (14.1%), thyroid (6.4%) and testicles (16.7%) were also frequently shielded, possibly reflecting an emphasis on shielding reproductive organs in children. TBI-RIST was performed more frequently than myeloablative conditioning in patients with benign disease. Genital and thyroid shielding were applied more frequently in patients treated with TBI-RIST than in patients treated with myeloablative conditioning. In conclusion, this study indicates the status of TBI-RIST in Japan and can assist future efforts to standardize TBI-RIST treatment methods and to design a future multicenter collaborative research study.

Patient preference study comparing hypofractionated versus conventionally fractionated whole-breast irradiation after breast-conserving surgery.

OBJECTIVE: To compare patient preferences and acute adverse events of hypofractionated (HF) and conventionally fractionated (CF) whole-breast irradiation (WBI) after breast-conserving surgery in our institution. METHODS: We conducted a patient preference study comparing CF-WBI (50 Gy/25 fractions) and HF-WBI (41.6 Gy/16 fractions) after breast-conserving surgery. Eligible patients selected either type of fractionation following an explanation from the radiation oncologist. In this report, we analyzed the selection rate and acute toxicities. RESULTS: Between June 2009 and December 2013, 348 patients (349 breasts) were identified as eligible for the study. Among them, 259 patients (260 breasts [74.5%]) selected CF-WBI and 89 patients (89 breasts [25.5%]) selected HF-WBI. Factors significantly associated with the selection of HF-WBI were older age (P = 0.028) and no adjuvant chemotherapy (P = 0.041). Regarding acute adverse events, Grade 2 (G2) or higher radiation dermatitis was less frequently observed in HF-WBI than in CF-WBI (13.8% vs. 29.4%; P = 0.004). In addition, G2 or higher breast pain was only observed in the CF-WBI group (6.9%; P = 0.012). There were no significant differences in the presence of fatigue, wound pain or radiation pneumonitis of G2 or higher between the groups. CONCLUSIONS: In this study, in which patients themselves selected the irradiation method, more patients tended to select CF-WBI. The frequency of G2 or higher dermatitis and breast pain was significantly lower in the HF-WBI group than in the CF-WBI group. Our results support the evidence for recommending HF-WBI after breast-conserving surgery while presenting aspects of patient preferences.

Additional chemotherapy improved local control and overall survival after stereotactic body radiation therapy for patients with oligo-recurrence.

BACKGROUND: Oligo-recurrence has been considered to confer improved prognosis than other oligometastatic conditions, and stereotactic body radiation therapy (SBRT) is considered as an option of local therapy for lung or liver metastases. The purpose of this study was to investigate the efficacy and safety of SBRT for lung and liver oligo-recurrent lesions and evaluate predictive factors for local control and prognosis. METHODS: This retrospective study included patients who presented with 1-3 matachronous lung or liver metastases, and treated with SBRT between May 2013 and March 2016 at a single institution. All patients harbored a controlled primary lesion. Patients with < 6 months of follow-up were excluded. Local control, progression free survival, and overall survival rates were analyzed according to the Kaplan-Meier product limit method. Univariable log-rank and multivariable Cox regression analyses were performed to clarify predictive factors for local control and prognosis. Toxicity was graded according to the Common Terminology Criteria for Adverse Events, version 4.0. RESULTS: Seventy-six patients with a total of 70 and 44 lung and liver lesions were included. The median follow-up period was 21 (range, 7-43) months. The 1-year local control, progression-free survival and overall survival rates were 89, 38 and 96%, respectively. Smaller gross tumor volume and additional chemotherapy after SBRT were significant predictive factors for better local control (p = 0.005 and p = 0.047), and the presence of a single metastatic lesion was a significant factor of good progression free survival (p = 0.008). Additional chemotherapy after SBRT was not a significant predictive factor but conferred to better overall survival (p = 0.078). Among colorectal cancer patients, post SBRT chemotherapy was significantly associated with better OS (p = 0.025). Over grade 3 adverse event was seen in only one patient. CONCLUSION: SBRT is a safe and effective treatment for patients with lung and liver oligo-recurrence. Additional chemotherapy after SBRT improved local control, and single metastatic lesion was a significant predictive factor of better PFS in this study. Among colorectal cancer patients, additional chemotherapy after SBRT significantly associated better OS.

National survey of myeloablative total body irradiation prior to hematopoietic stem cell transplantation in Japan: survey of the Japanese Radiation Oncology Study Group (JROSG).

A myeloablative regimen that includes total-body irradiation (TBI) before hematopoietic stem cell transplantation results in higher patient survival rates than achieved with regimens without TBI. The TBI protocol, however, varies between institutions. In October 2015, the Japanese Radiation Oncology Study Group initiated a national survey of myeloablative TBI (covering 2010-2014). Among the 186 Japanese institutions performing TBI, 90 (48%) responded. The 82 institutions that had performed myeloablative TBI during this period treated 2698 patients with malignant disease [leukemia (2082 patients, 77.2%), malignant lymphoma (378, 14%)] and 37 with non-malignant disease [severe aplastic anemia (20, 54%), inborn errors of metabolism (5, 14%)]. A linear accelerator was used at all institutions. The institutions were divided into 41 large and 41 small institutions based on the median number of patients. The long source-surface distance technique was the method of choice in the 34 institutions (82.9%) and the moving-couch technique in the 7 (17.1%) in the large institutions. The schedules most routinely used by the participating institutions consisted of 12 Gy/6 fractions/3 days (26 institutions, 63.5%) in the large institutions. The dose rate varied from 5 to 26 cGy/min. The lungs and lenses were routinely shielded in 23 large institutions (56.1%), and only the lungs in 9 large institutions (21.9%). At lung-shielding institutions, the most frequent maximum acceptable total dose for the lungs was 8 Gy (19 institutions, 27.5%). Our results reveal considerable differences in the TBI methods used by Japanese institutions and thus the challenges in designing multicenter randomized trials based on TBI.

Ruthenium sensitizers with a hexylthiophene-modified terpyridine ligand for dye-sensitized solar cells: synthesis, photo- and electrochemical properties, and adsorption behavior to the TiO2 surface.

Two novel ruthenium sensitizers with a hexylthiophene-modified terpyridine ligand (TUS-35 and TUS-36) were synthesized to improve the molar absorptivity of the previously reported ruthenium sensitizer (TBA)[Ru{4'-(3,4-dicarboxyphenyl)-4,4″-dicarboxyterpyridine}(NCS)3], TBA = tetrabutylammonium (TUS-21). A relatively strong absorption appeared at ∼380 nm, and the molar absorption coefficient at the metal-to-ligand charge transfer (MLCT) band decreased in TUS-35 by introducing a 2-hexylthiophene unit to the 5-position of the terpyridine-derived ligand. For comparison, a relatively strong absorption was observed at ∼350 nm without decreasing the molar absorption coefficient at the MLCT band in TUS-36 by introducing a 2-hexylthiophene unit to the 4-position of the terpyridine-derived ligand. On the other hand, the energy levels of the highest occupied molecular orbitals and the lowest unoccupied molecular orbitals of these two sensitizers were found to be almost equal to those of TUS-21. The adsorption behavior of TUS-35 and TUS-36 was similar to that of (TBA)[Ru{4'-(3,4-dicarboxyphenyl)terpyridine}(NCS)3] (TUS-20), which binds to the TiO2 surface by using the 3,4-dicarboxyphenly unit, rather than that of TUS-21, which adsorbs to the TiO2 photoelectrode using one of the carboxyl groups at the terminal pyridines of the terpyridine-derived ligand. Therefore, TUS-35 and TUS-36 are considered to bind to the TiO2 surface by using the 3,4-dicarboxyphenly unit just like TUS-20. The dye-sensitized solar cells (DSCs) with TUS-35 and TUS-36 showed a relatively lower conversion efficiency (6.4% and 5.7%, respectively) compared to the DSC with TUS-21 (10.2%). Open-circuit photovoltage decay and electrochemical impedance spectroscopy measurements revealed that the promoted charge recombination and/or charge transfer of the injected electrons in the TiO2 photoelectrode is a main reason for the inferior performances of TUS-35 and TUS-36.

High signal intensity in the dentate nucleus and globus pallidus on unenhanced T1-weighted MR images: relationship with increasing cumulative dose of a gadolinium-based contrast material.

PURPOSE: To explore any correlation between the number of previous gadolinium-based contrast material administrations and high signal intensity (SI) in the dentate nucleus and globus pallidus on unenhanced T1-weighted magnetic resonance (MR) images. MATERIALS AND METHODS: The institutional review board approved this study, waiving the requirement to obtain written informed consent. A group of 381 consecutive patients who had undergone brain MR imaging was identified for cross-sectional analysis. For longitudinal analysis, 19 patients who had undergone at least six contrast-enhanced examinations were compared with 16 patients who had undergone at least six unenhanced examinations. The mean SIs of the dentate nucleus, pons, globus pallidus, and thalamus were measured on unenhanced T1-weighted images. The dentate nucleus-to-pons SI ratio was calculated by dividing the SI in the dentate nucleus by that in the pons, and the globus pallidus-to-thalamus SI ratio was calculated by dividing the SI in the globus pallidus by that in the thalamus. Stepwise regression analysis was undertaken in the consecutive patient group to detect any relationship between the dentate nucleus-to-pons or globus pallidus-to-thalamus SI ratio and previous gadolinium-based contrast material administration or other factors. A random coefficient model was used to evaluate for longitudinal analysis. RESULTS: The dentate nucleus-to-pons SI ratio showed a significant correlation with the number of previous gadolinium-based contrast material administrations (P < .001; regression coefficient, 0.010; 95% confidence interval [CI]: 0.009, 0.011; standardized regression coefficient, 0.695). The globus pallidus-to-thalamus SI ratio showed a significant correlation with the number of previous gadolinium-based contrast material administrations (P < .001; regression coefficient, 0.004; 95% CI: 0.002, 0.006; standardized regression coefficient, 0.288), radiation therapy (P = .009; regression coefficient, -0.014; 95% CI: -0.025, -0.004; standardized regression coefficient, -0.151), and liver function (P = .031; regression coefficient, 0.023; 95% CI: 0.002, 0.044; standardized regression coefficient, 0.107). The dentate nucleus-to-pons and globus pallidus-to-thalamus SI ratios in patients who had undergone contrast-enhanced examinations were significantly greater than those of patients who had undergone unenhanced examinations (P < .001 for both). CONCLUSION: High SI in the dentate nucleus and globus pallidus on unenhanced T1-weighted images may be a consequence of the number of previous gadolinium-based contrast material administrations.

Characterization of photovoltaic performance of the dye-sensitized solar cell with a novel ruthenium complex having a bisdemethoxycurcumin as a ligand.

The first example of a ruthenium sensitizer (TUS-22) having a natural dye, bisdemethoxycurcumin, as a ligand has been synthesized. The dye-sensitized solar cell based on this novel dye showed 5.8% conversion efficiency under AM 1.5 (100 mW/cm(2)) irradiation.

Minichromosome maintenance 2 (MCM2) immunoreactivity in stage III human gastric carcinoma: clinicopathological significance.

BACKGROUND: The origin licensing factor minichromosome maintenance 2 (MCM2) has recently been identified as a critical regulator of proliferation in both normal and neoplastic cells. This study examined whether MCM2 expression was of prognostic relevance in patients with stage III gastric carcinoma and whether the expression of this marker showed any correlation with clinicopathological characteristics. In addition, we evaluated whether the expression of this proliferation marker was correlated with that of another marker, Ki-67, in gastric carcinoma. METHODS: We examined the immunohistochemical expression of MCM2, Ki-67, and p53 in 103 surgically removed stage III gastric carcinomas, which consisted of 60 intestinal-type and 43 diffuse-type carcinomas. The labeling indices (LIs) of MCM2 and Ki-67 in cancer cells were compared with clinicopathological characteristics, p53 expression, and overall survival rates. RESULTS: The mean MCM2 and Ki-67 LIs were 69.1 +/- 11.8% and 48.2 +/- 14.5%, respectively, in the intestinal carcinomas, and 43.7 +/- 9.9% and 24.9 +/- 11.0%, respectively, in the diffuse carcinomas. The LIs of these proteins revealed no significant association with clinicopathological characteristics or with p53 expression in the carcinomas. Kaplan-Meier survival curves showed that, in the patients with diffuse carcinoma, those with higher MCM2 LIs had a poorer prognosis (P < 0.05), but the MCM2 LI was not correlated with prognosis for those with intestinal carcinoma (P = 0.25). Ki-67 expression had no significant correlation with prognosis in either intestinal-type or diffuse-type carcinomas. Multivariate Cox regression analysis confirmed that MCM2 was an independent prognostic factor in patients with diffuse carcinoma. CONCLUSION: Our data suggest that MCM2 is a useful prognostic marker in patients stage III diffuse-type gastric carcinoma.