Treatment planning of carbon ion radiotherapy for prostate cancer based on cellular experiments with PC3 human prostate cancer cells.

[Purpose] Treatment plans for carbon ion radiotherapy (CIRT) in Japan are designed to uniformly deliver the prescribed clinical dose based on the radiosensitivity of human salivary gland (HSG) cells to the planning target volume (PTV). However, sensitivity to carbon beams varies between cell lines, that is, it should be checked that the clinical dose distribution based on the cell radiosensitivity of the treatment site is uniform within the PTV. [Methods] We modeled the linear energy transfer (LET) dependence of the linear-quadratic (LQ) coefficients specific to prostate cancer, which accounts for the majority of CIRT. This was achieved by irradiating prostate cancer cells (PC3) with X-rays from a 4 MV-Linac and carbon beams with different LETs of 11.1-214.3 keV/µm. By using the radiosensitivity of PC3 cells derived from cellular experiments, we reconstructed prostate-cancer-specific clinical dose distributions on patient computed tomography (CT). [Results] The LQ coefficient, α, of PC3 cells was larger than that of HSG cells at low (<50 keV/µm) LET and smaller at high (>50 keV/µm) LET, which was validated by cellular experiments performed on rectangular SOBPs. The reconstructed dose distribution on patient CT was sloped when 1 fraction incident from the one side of the patient was considered, but remained uniform from the sum of 12 fractions of the left-right opposing beams (as is used in clinical practice). [Conclusion] Our study reveals the inhomogeneity of clinical doses in single-field plans calculated using the PC3 radiosensitivity data. However, this inhomogeneity is compensated by using the combination of left-right opposing beams.

Effects of dietary vitamin K3 supplementation on vitamin K1 and K2 (menaquinone) dynamics in dairy cows.

The effect of dietary vitamin K3 (VK3) on ruminant animals is not fully investigated. The aim of this study was to examine the effects of dietary VK3 on lactation performance, rumen characteristics, and VK1 and menaquinone (MK, or VK2) dynamics in the rumen, plasma, and milk of dairy cows. Eight Holstein dairy cows in late lactation periods were used in two crossover trials including a control (nontreatment) and a 50 or 200 mg/day (d) VK3 supplementation group. After 14 days, plasma, ruminal fluid, and milk were sampled and their VK1 and MKs contents were measured using fluorescence-high-performance liquid chromatography (HPLC). Milk production was unchanged after feeding 50 mg/day VK3 but marginally decreased after feeding 200 mg/day VK3. The molar ratio of propionate in ruminal fluid was significantly increased on feeding 200 mg/day VK3. Additionally, MK-4 concentrations significantly increased in both plasma and milk after VK3 feeding (50 and 200 mg/day). In ruminal fluid, MK-4 concentrations increased after 200 mg/day VK3 feeding. These results suggest that VK3 may be a good source of MK-4, the biologically active form of VK, in Holstein dairy cows during their late lactation periods. This study provides a basis for understanding the physiological role of VK in dairy cows.

Role of CD8 T-cell in immune response to tuberculosis-specific antigen in QuantiFERON-TB Gold Plus.

Recent contacts with active TB (tuberculosis) patients were screened for latent tuberculosis infection (LTBI) because of their greater relative risk for developing active TB. QuantiFERON®-TB Gold Plus (QFT-Plus) offers two TB-specific antigen tubes (TB1 and TB2). TB1 elicits CD4 T-cell responses, and TB2 is designed to elicit both CD4 and CD8 T-cell responses. These mechanisms could be useful for estimating the role of CD8 T-cell immune responses to TB-specific antigens. To estimate the QFT-Plus capability to diagnose LTBI, a prospective cross-sectional study was conducted. A total of 412 TB contacts (median age 44 years) were enrolled. The positivity rates of QFT-Plus, TB1 and TB2 were 7.5%, 6.3% and 7.2%, respectively. TB2 showed a higher positivity rate compared to TB1, but without significant difference. The interferon (IFN)-γ productions of TB1 and TB2 were well correlated (r = 0.934, P < 0.001). The ratio of IFN-γ production between TB1 and TB2 showed a median (interquartile range) of IFN-γ[QFT-Plus TB2]/IFN-γ[QFT-Plus TB1] of 1.09 (0.91-1.36). CD8 T-cell immune response to TB-specific antigens varied among subjects. CD8 T-cell potentially boosts IFN-γ productions in QFT-Plus and results in the detection of more persons with LTBI. However, there was no significant difference in the positivity rates of QFT-Plus TB1 and TB2 in our TB contact investigation. The contribution of CD8 T-cells might be small for the diagnosis of LTBI. The analysis of IFN-γ production in both TB1 and TB2 would lead to further analysis of the TB immune response, and especially that caused by CD8 T-cells.

Variation in interferon-γ production between QFT-Plus and QFT-GIT assays in TB contact investigation.

BACKGROUND: Individuals with recent contact with active tuberculosis (TB) patients were screened for latent tuberculosis infection (LTBI) considering their greater relative risk for developing active TB. QuantiFERON®-TB Gold Plus (QFT-Plus) assay offers two TB-specific antigen tubes (TB1 and TB2). TB2 is designed to elicit both CD4 and CD8 T-cell responses. This mechanism could lead to increased sensitivity as compared to the QuantiFERON®-TB Gold In-Tube (QFT-GIT) assay. Our objective was to compare the LTBI diagnostic capability of QFT-Plus with that of QFT-GIT. METHODS: A total of 412 TB contacts (median age 44 years) were prospectively enrolled. We conducted both QFT-Plus and QFT-GIT assays concurrently. We also analyzed production of interferon-γ (IFN-γ) in response to TB-specific antigens. RESULTS: The positivity rates in QFT-Plus and QFT-GIT were 7.5% (95% confidence interval (CI), 5.4-10.5) and 5.8% (CI, 3.9-8.5), respectively, showing a significant difference (P < 0.05). The median (inter-quartile range [IQR]) of IFN-γ[QFT-Plus]/IFN-γ[QFT-GIT] was 1.41 (1.00-2.00). QFT-Plus produced 1.4 times IFN-γ. CONCLUSIONS: QFT-Plus revealed significantly higher positivity rate compared with QFT-GIT, which might be attributed to increased IFN-γ production. The cut-off in both QFT-Plus and QFT-GIT was 0.35 IU/mL. These effects might resulted in the higher positivity rate in QFT-Plus.

A case of basaloid carcinoma of the esophagus with a solitary lung metastasis for which thoracoscopic partial lung resection was performed.

We experienced a case of basaloid carcinoma of the esophagus with a solitary lung metastasis for which thoracoscopic partial lung resection was performed. To the best of our knowledge, this is the first reported case of basaloid carcinoma of the esophagus with lung metastasis for which surgery was performed. There are no evidence-based treatment strategies for postoperative recurrence of basaloid carcinoma of the esophagus. Treatment strategies such as adjuvant therapy centered on chemotherapy and surgical indications should be established.

[Lung metastasis of basaloid-squamous cell carcinoma of the esophagus; report of a case].

A 69-year-old woman had undergone a subtotal esophagectomy for basaloid-squamous cell carcinoma of the esophagus 2 years before (pT3, ly1, v2, pN0, pStage II). Right lung metastasis was detected by follow up chest computed tomography( CT). A partial resection of the right lung was performed. Histopathological diagnosis was basaloid-squamous cell carcinoma. She is doing well 17 months after surgery for metastasis.To our knowledge, no case of radical surgery for the lung metastasis of basaloid-squamous cell carcinoma has not been reported in the Japanese literature to date.

Clear cell tumor of the lung: surgical and immunohistochemical findings.

We encountered a clear cell tumor of the lung (CCTL) that was located peripherally, adjacent to the visceral pleura. The tumor could be directly observed during surgery. We believe that this case report describing the surgical and related pathological findings is highly informative. A chest radiograph during routine examination of an asymptomatic 65-year-old woman being treated for hypertension and hyperlipidemia revealed a nodular shadow in the left lung field. Wedge resection was performed by video-assisted thoracic surgery. The in vivo color of the tumor was red, suddenly changing to white after the tumor was clamped. Pathology examination showed a uniform pattern consisting of large clear cells without cytologic atypia or increased mitotic activity. Immunohistochemistry revealed tumor cells positive for vimentin and melanocytic markers (HMB-45 and melan-A) and negative for epithelial membrane antigen and cytokeratin. With the absence of clinical findings in both kidneys, the tumor was diagnosed as a benign CCTL.

Metaplastic carcinoma of the breast.

The purposes of this study were to investigate whether the biological characteristics or outcomes of patients with metaplastic carcinoma, invasive ductal carcinoma, or invasive lobular carcinoma of the breast differ; to determine whether the metaplastic carcinoma subtypes have similar malignant potentials; and to identify accurate predictors of outcome in patients with metaplastic carcinoma. The subject comprised 6137 invasive ductal carcinoma patients, 301 invasive lobular carcinoma patients, and 46 metaplastic carcinoma patients of the breast. The metaplastic carcinomas were classified according to the World Health Organization classification. Multivariate analyses clearly demonstrated that the metaplastic carcinoma patients had a significantly poorer outcome than the invasive ductal carcinoma patients or the invasive lobular carcinoma patients independent of the nodal status or age not exceeding 39 years, whereas patients with triple-negative metaplastic carcinomas or triple-negative invasive lobular carcinomas had a poorer outcome than those with triple-negative invasive ductal carcinomas. Although no significant differences in clinical outcome were observed among the metaplastic carcinoma subtypes in multivariate analyses, an age not exceeding 39 years, the presence of skin invasion, and the presence of a squamous cell carcinoma component in nodal tumors were significant outcome predictors for metaplastic carcinoma patients. In conclusion, the results of this study clearly demonstrated that metaplastic carcinoma is more aggressive than invasive ductal carcinoma or invasive lobular carcinoma. Although the metaplastic carcinoma subtypes had no prognostic significance, an age not exceeding 39 years, the presence of skin invasion, and the presence of a squamous cell carcinoma component in nodal tumors were significant predictors of outcome among metaplastic carcinoma patients.

Grading system for lymph vessel tumor emboli: significant outcome predictor for patients with invasive ductal carcinoma of the breast who received neoadjuvant therapy.

The purpose of this study was to confirm that the grades of lymph vessel tumor emboli in biopsy specimens obtained before neoadjuvant therapy and in the surgical specimens obtained after neoadjuvant therapy according to the grading system we devised are significant histological outcome predictor for invasive ductal carcinoma (IDC) patients who received neoadjuvant therapy. The subjects of this study were the 318 consecutive IDC patients who had received neoadjuvant therapy in our institution. The lymph vessel tumor embolus grades in the biopsy specimens and in the surgical specimens were significantly associated with the increases in mean number of nodal metastases. Multivariate analyses with well-known prognostic factors and p53 expression in tumor-stromal fibroblasts clearly showed that the lymph vessel tumor embolus grade based on the biopsy specimens and based on the surgical specimens significantly increased the hazard rates for tumor recurrence and tumor-related death in all the IDC patients as a whole, in the IDC patients who did not have nodal metastasis, and in the IDC patients who had nodal metastasis, and the outcome-predictive power of the lymph vessel tumor embolus grades based on the surgical specimens was superior to that of the lymph vessel tumor embolus grades based on the biopsy specimens. The grades in the grading system for lymph vessel tumor emboli were significantly associated with nodal metastasis, and the histological grading system is an excellent system for accurately predicting the outcome of patients with IDC of the breast who have received neoadjuvant therapy.

Grading system for lymph vessel tumor emboli: significant outcome predictor for invasive ductal carcinoma of the breast.

The purpose of this study was to confirm that the grading system for lymph vessel tumor emboli is a significant histologic outcome predictor for patients with invasive ductal carcinoma. The subjects of this study were 1042 invasive ductal carcinoma patients who did not receive neoadjuvant therapy. We classified all invasive ductal carcinomas according to the grading system for lymph vessel tumor emboli we devised, and performed multivariate analyses with well-known prognostic factors. Of 1042 carcinomas, 666, 250, 97, and 29 were classified according to the grading system for lymph vessel tumor emboli as grade 0 (no lymph vessel invasion), grade 1, grade 2, and grade 3, respectively. The univariate analyses showed that the difference in outcome between the group with grade 0 and the group with grade 1 was not significant, but that survival time was significantly shorter in the group of patients with grade 2 carcinomas than in the group with grade 1 carcinomas and significantly shorter in the group of patients with grade 3 carcinomas than in the group with grade 2 carcinomas. Multivariate analyses demonstrated that having a grade 2 or grade 3 carcinoma significantly increased the hazard rates for tumor recurrence and tumor-related death in the patients as a whole as well as in both the group of patients with nodal metastasis and the group without nodal metastasis. The grading system for lymph vessel tumor emboli is an excellent histologic grading system for predicting the outcome of patients with invasive ductal carcinoma of the breast.

p53 expression in tumor-stromal fibroblasts is closely associated with the nodal metastasis and outcome of patients with invasive ductal carcinoma who received neoadjuvant therapy.

The purpose of this study was to determine whether p53 immunoreactivity in tumor-stromal fibroblasts assessed by the Allred scoring system in biopsy specimens obtained before neoadjuvant therapy and assessed in surgical specimens obtained after neoadjuvant therapy is significantly associated with nodal metastasis by invasive ductal carcinoma and with the outcome of 318 patients with invasive ductal carcinoma who received neoadjuvant therapy, according to UICC pathologic TNM stage, in multivariate analyses with well-known clinicopathologic factors. The Allred scores for p53 in tumor-stromal fibroblasts in the surgical specimens were significantly associated with the presence of nodal metastasis. The Allred scores for p53 in the tumor-stromal fibroblasts of biopsy and surgical specimens were a very important outcome predictive factor for patients who received neoadjuvant therapy, independent of UICC pathologic TNM status, but the outcome predictive power of the Allred scores for p53 in tumor-stromal fibroblasts assessed in the surgical specimens was superior to that of the Allred scores for p53 in tumor-stromal fibroblasts in the biopsy specimens. The results indicated a close association between p53 protein expression in tumor-stromal fibroblasts, especially in surgical specimens, and both the presence of nodal metastasis and the outcome of invasive ductal carcinoma patients who received neoadjuvant therapy.

p53 expression in tumor stromal fibroblasts is associated with the outcome of patients with invasive ductal carcinoma of the breast.

The purpose of this study was to determine whether p53 protein expression in tumor stromal fibroblasts assessed immunohistochemically by the Allred score system is significantly associated with nodal metastasis by invasive ductal carcinoma (IDC), and significantly associated with the outcome of 1042 IDC patients according to adjuvant therapy status, UICC pTNM stage, and triple-negative IDC status, in multivariate analyses with well-known clinicopathological factors. The Allred scores for p53 expression in tumor stromal fibroblasts were significantly associated with the number of nodal metastases, and Allred scores of 4-8 for p53 in tumor stromal fibroblasts significantly increased the hazard rate for distant organ metastasis or for tumor death in the triple-negative IDC patients, and the UICC pTNM stage I, II, and III patients. The results indicated that p53 protein expression in tumor stromal fibroblasts is closely associated with the number of nodal metastases and the outcome of IDC patients.

Delayed diagnosis of traumatic diaphragmatic rupture.

We report a case of late presentation of traumatic rupture of the diaphragm discovered incidentally on chest radiography (CXR) during an annual medical checkup. A 60-year-old man suffered severe blunt trauma from heavy steel frames collapsing against his back, resulting in pelvic and femoral fractures as well as pulmonary contusions. The patient recovered, but 10 months later CXR performed for lung cancer surveillance during an annual medical checkup revealed a traumatic rupture of the diaphragm. Video-assisted thoracic surgery was performed with reduction of the intestine and primary closure of the diaphragmatic defect. The patient recovered uneventfully. This report serves as a useful reminder that a medical history of severe blunt trauma should provoke a high index of suspicion for diaphragmatic rupture during annual medical surveillance.

Tumor histology in lymph vessels and lymph nodes for the accurate prediction of outcome among breast cancer patients treated with neoadjuvant chemotherapy.

The present study investigated fibrotic foci (FFs), the grading system for lymph vessel tumor emboli (LVTEs), and the histological characteristics of nodal metastatic tumors that were significantly associated with the outcomes of 115 patients with invasive ductal carcinoma (IDC) who had received neoadjuvant chemotherapy. We compared the outcome predictive power of FFs, the grading system for LVTEs, and the histological characteristics of metastatic tumors in lymph nodes with the well-known clinicopathological characteristics of tumor recurrence and tumor-related death in multivariate analyses. The presence of FFs, as assessed by a biopsy performed before neoadjuvant chemotherapy, significantly increased the hazard rates (HRs) for tumor-related death in all the cases and in cases with nodal metastasis. The grading system for LVTEs, which was assessed using surgical specimens obtained after neoadjuvant chemotherapy, was significantly associated with increasing hazard rates (HRs) for tumor recurrence and tumor-related death in all the cases and in cases with nodal metastasis. Moderate to severe stroma in nodal metastatic tumors and five or more mitotic figures in nodal metastatic tumors were significantly associated with elevated HRs for tumor recurrence and tumor-related death among all the cases. These results indicated that FFs, the grading system for LVTEs, and the histological characteristics of tumor cells in lymph nodes play important roles in predicting the tumor progression of IDCs of the breast in patients treated with neoadjuvant chemotherapy.