Proton beam therapy for hepatocellular carcinoma

BACKGROUND:

The authors have published a series of studies evaluating the safety and efficacy of proton beam therapy for the treatment of hepatocellular carcinoma in a variety of clinical settings. In the current study, they retrospectively reviewed their entire experience treating hepatocellular carcinoma patients with proton beam therapy at their hospital‐based facility at the University of Tsukuba.

METHODS:

From November 2001 to December 2007, 333 patients with hepatocellular carcinoma were treated with proton beam therapy at the University of Tsukuba. A total of 318 patients were included in this study. Total dose delivered and fractionation scheme were determined by protocols that varied based on location of tumor. Survival rates and prognostic factors were assessed.

RESULTS:

Overall actuarial survival rates at 1‐year, 3‐years, and 5‐years were 89.5% (95% confidence interval [95% CI], 85.7‐93.1%), 64.7% (95% CI, 56.6‐72.9%), and 44.6% (95% CI, 29.7‐59.5%), respectively. Child‐Pugh liver function (hazards ratio [HR], 2.84; P < .01), T stage (HR, 1.94; P < .05), performance status (HR, 2.12; P < .01), and planning target volume (HR, 2.12; P < .05) significantly impacted survival. The 3‐year and 5‐year survival rates were 69.1% (95% CI, 59.9‐78.3%) and 55.9% (95% CI, 41.5‐70.3%), respectively, for patients with Child‐Pugh A disease and 51.9% (95% CI, 32.3‐71.5%) and 44.5% (95% CI, 23.1‐65.8%), respectively, for patients with Child‐Pugh B disease. The actuarial survival rates of patients with Child‐Pugh class A were statistically different between groups of planned target volume ≤125 mL and >125 mL (P < .05).

CONCLUSIONS:

The authors have shown proton beam therapy to be both safe and effective for the treatment of patients with hepatocellular carcinoma. They strongly recommend the consideration of proton beam therapy in patients for whom other treatment options are risky or contraindicated. Cancer 2009. © 2009 American Cancer Society.     

Efficacy of the combined use of bevacizumab and irinotecan as a postoperative adjuvant chemotherapy in colon carcinoma

We evaluated the efficacy of anti-human VEGF antibody (bevacizumab) with or without irinotecan (CPT-11) against lung metastases in which neovascularization was already induced, as a postoperative adjuvant therapy using orthotopically implanted colon cancer in rat. The high VEGF productive KM12SM human colon cancer cells were injected into the cecal wall. At 5 weeks after the injection, the cecum was removed including the tumor. Then, 5 mg/kg of bevacizumab and 40 mg/kg of CPT-11 were administered, alone or in combination, intravenously once a week for 3 weeks, from day 15 after the cecal removal. The results show that the incidences of macroscopic and/or microscopic lung metastases in the bevacizumab-alone group (B) and in the combination group (C) were significantly lower (B, p=0.001 and C, p=0.037) than that in the control group at day 35 after the cecal removal. The number of lung metastases in B was 0.8+/-0.8 (p=0.024) and in C 2.4+/-1.8 (p=0.060), each value lower than the 12.4+/-4.2 of the control group. The growth of a subcutaneously implanted tumor was significantly inhibited in the combination group compared to either the CPT-alone (p=0.003) or the bevacizumab-alone groups (p=0.027). Apoptosis was significantly (p<0.001) induced in the combination group. In conclusion, a beneficial effect of bevacizumab against postoperative lung metastases may be expected even after the establishment of neovascularization in metastatic foci in nude rat. The results from the present subcutaneously implanted tumor model suggested that a higher efficacy may be expected when bevacizumab is combined with the cytotoxic agent CPT-11, compared to bevacizumab alone, against tumors with a variety of VEGF production levels in clinical situations.     

Proton beam therapy for hepatocellular carcinoma adjacent to the porta hepatis

PURPOSE: To evaluate the efficacy and safety of proton beam therapy (PBT) for patients with hepatocellular carcinoma (HCC) located adjacent to the porta hepatis. METHODS AND MATERIALS: Subjects of the study were 53 patients with HCC located within 2 cm of the main portal vein. All patients had tumor confined to the radiation field with no evidence of metastatic disease. All patients had hepatic function levels of a Child-Pugh score of 10 or less, Eastern Cooperative Oncology Group performance status of 2 or less, and no uncontrolled ascites. Patients underwent PBT of 72.6 GyE in 22 fractions from Sept 2001 to Dec 2004. RESULTS: After 3 years, the actuarial survival rate was 45.1% and local control rate was 86.0%. Prognostic factors for survival included Child-Pugh score, number of tumors, and alpha-fetoprotein levels. No late treatment-related toxicity of Grade 2 or higher was observed. CONCLUSIONS: The PBT delivering 72.6 GyE in 22 fractions appears to be effective and safe for HCC adjacent to the porta hepatis.     

Paraganglioma of the posterior mediastinum diagnosed by immunohistochemical staining

Paraganglioma of the mediastinum are rare neoplasms. To date, no definitive morphologic criteria exist that correlate with the clinical outcome of these tumors. We have encountered a case of paraganglioma in which biological behavior was assessed by immunohistochemical staining to determine whether supplementary postoperative treatment was needed. A 28-year-old man came to our hospital because of an abnormal shadow on a radiogram of the chest. He had no symptoms. Hematological findings were unremarkable. Diagnostic imaging suggested a neurogenic tumor. Surgical resection was performed in September, 2002. A typical nesting pattern (Zellballen) and positivity for chromogranin on immunohistochemical staining were evident, indicating neuroendocrine characteristics, and paraganglioma was diagnosed. Tissue specimens indicated an MIB-1-labeling index of 1.3% on MIB-1 staining, and a relatively well maintained distribution of S-100 protein-positive sustentacular cells, which were suggestive of a benign tumor. The patient did not receive any supplementary therapy postoperatively but was given careful follow-ups.     

Pilot study on probe-based confocal laser endomicroscopy for colorectal neoplasms: an initial experience in Japan

Background

The aim of this pilot study is to investigate the diagnostic yield of probe-based confocal laser endomicroscopy (pCLE) in the evaluation of depth of invasion in colorectal lesions.

Methods

Patients with colorectal lesions eligible for either endoscopic treatment or surgery were enrolled in the study. Tumor’s depth of invasion was classified as mucosal or slight submucosal (M-SM1) and deep submucosal invasion or deeper (SM2 or deeper). White light endoscopy (WLE), magnifying narrow band imaging (M-NBI), and magnifying chromoendoscopy (M-CE) were used to assess colorectal lesions, and pCLE was used to identify tumor’s features related to SM2 or deeper. The diagnostic classification of depth of invasion was obtained by correlating pCLE findings with histology results (on-site diagnosis). All colorectal lesions were stratified by a second endoscopist who was blinded to any clinical and histological information with the use of WLE, M-NBI, M-CE, and pCLE (off-line review).

Results

A total of 22 colorectal lesions were analyzed: seven were adenoma, ten intramucosal cancer, and five SM2 or deeper cancer. With respect to pCLE findings, loss of crypt structure was seen in all SM2 or deeper cancers and only in one M-SM1 lesion. Sensitivity, specificity, and accuracy of WLE, M-NBI, and M-CE in off-line review were 60/94/86, 60/94/86, and 80/94/91%, respectively. Sensitivity/specificity/accuracy of pCLE in off-line review were 80/94/91%, respectively. The inter-observer agreement of pCLE between on-site diagnosis and off-line review was 0.64 (95%CI 0.27–1.0).

Conclusions

pCLE may represent a useful tool to evaluate the depth of invasion in colorectal lesions.

     

Developmental and age-related changes to the elastic lamina of Bruch’s membrane in mice

Graefe's Archive for Clinical and Experimental Ophthalmology - Fibrillin-1, tropoelastin, fibulin-5, and latent transforming growth factor beta-binding protein-2 and protein-4 (LTBP-2 and...     

Effect of TA-270, a novel quinolinone derivative, on antigen-induced nasal blockage in a guinea pig model of allergic rhinitis

TA-270 (4-hydroxy-1-methyl-3-octyloxy-7-sinapinoylamino-2(1H)-quinolinone) is a novel quinolinone derivative that has been demonstrated to possess an anti-oxidative activity against peroxynitrite, a potent oxidant, that is generated by the reaction of nitric oxide with superoxide anions. The current study describes the inhibitory effect of TA-270 on the biphasic nasal blockage induced by repeated antigen challenge in an allergic rhinitis guinea pig model. In the present in vitro study, TA-270 potently inhibited the oxidative reaction induced by peroxynitrite (IC₅₀ = 79 nM). In addition, TA-270 (0.3-30 mg/kg, p.o.) dose-dependently inhibited peroxynitrite (3 mM, 10 μl/nostril)-induced nasal blockage in guinea pigs. In the antigen-induced allergic rhinitis model, TA-270 (0.3, 3, and 30 mg/kg, p.o.) given 1 h before the antigen challenge suppressed early phase nasal blockage by 36%, 42%, and 63%, respectively. Furthermore, TA-270 (0.3, 3, and 30 mg/kg, p.o.) showed a relatively strong suppression of late phase nasal blockage (39%, 62%, and 72%, respectively). The late phase nasal blockage was significantly inhibited (61%) even when TA-270 (30 mg/kg, p.o.) was administered 18 h before the antigen challenge. In conclusion, TA-270 improved antigen-induced nasal blockage, probably through its peroxynitrite scavenging action, and the effect was sustained for at least 18 h. Thus, TA-270 would be expected to relieve nasal blockage in allergic rhinitis patients.     

Presence of a family history and excessive pressure on the first toe pad during walking in female subjects with pincer nails

Pincer nails (PN) are defined as a transverse overcurvature of the nail plate. Although there have been advancements in therapeutic approaches, the precise underlying mechanisms for the development of PN are still not fully understood. Currently, PN are assumed to develop due to lack of upward mechanical force on the toes. We developed a novel wireless device to observe detailed gait motion. We analyzed trends of gait motion in healthy individuals without PN, healthy individuals with PN without a family history of PN, and healthy individuals with PN and a family history of PN. We found that a family history of PN is an independent risk factor for PN, irrespective of gait motion. Moreover, healthy individuals with PN but without a family history of PN exhibit strong and concentrated pressure on the first toe pad during walking. In sum, a family history of PN and excess upward mechanical forces on the first toe pad during walking may be risk factors for the development of PN.