Comparison of intensity-modulated radiotherapy with the 5-field technique,helical tomotherapy and volumetric modulated arc therapy for localized prostate cancer

The outcomes of three methods of intensity-modulated radiation therapy (IMRT) for localized prostate cancer were evaluated. Between 2010 and 2018, 308 D’Amico intermediate- or high-risk patients were treated with 2.2 Gy daily fractions to a total dose of 74.8 Gy in combination with hormonal therapy. Overall, 165 patients were treated with 5-field IMRT using a sliding window technique, 66 were then treated with helical tomotherapy and 77 were treated with volumetric modulated arc therapy (VMAT). The median age of patients was 71 years. The median follow-up period was 75 months. Five-year overall survival (OS) and biochemical or clinical failure-free survival (FFS) rates were 95.5 and 91.6% in the 5-field IMRT group, 95.1 and 90.3% in the tomotherapy group and 93.0 and 88.6% in the VMAT group, respectively, with no significant differences among the three groups. The 5-year cumulative incidence of late grade ≥2 genitourinary and gastrointestinal toxicities were 7.3 and 6.2%, respectively, for all patients. Late grade ≥2 gastrointestinal toxicities were less frequent in patients undergoing VMAT (0%) than in patients undergoing 5-field IMRT (7.3%) and those undergoing tomotherapy (11%) (P = 0.025), and this finding appeared to be correlated with the better rectal DVH parameters in patients undergoing VMAT. Other toxicities did not differ significantly among the three groups, although bladder dose-volume parameters were slightly worse in the tomotherapy group than in the other groups. Despite differences in the IMRT delivery methods, X-ray energies and daily registration methods, all modalities may be used as IMRT for localized prostate cancer.     

Combining the Tumor Contact Length and Apparent Diffusion Coefficient Better Predicts Extraprostatic Extension of Prostate Cancer with Capsular Abutment: A 3 Tesla MR Imaging Study

Purpose: To assess the diagnostic performance of the tumor contact length (TCL) and apparent diffusion coefficient (ADC) for predicting extraprostatic extension (EPE) of prostate cancer with capsular abutment (CA).Methods: Ninety-three patients with biopsy-proven prostate cancer underwent 3-Tesla MRI, including diffusion-weighted imaging (b value = 0, 2000 s/mm²) and radical prostatectomy. Two experienced radiologists, blinded to the clinicopathological data, retrospectively assessed the presence of CA on T2-weighted imaging (T2WI). TCL on T2WI and ADC values were measured on detecting CA in prostate cancer. We used the receiver operating characteristic curves to assess the diagnostic performance of TCL and ADC values for predicting EPE.Results: CA was present in 58 prostate cancers among 93 patients. The cut-off value for TCL was 6.9 mm, which yielded an area under the curve (AUC) of 0.75. This corresponded to a sensitivity, specificity, and accuracy of 84.2%, 61.5%, and 69.0%, respectively. The cut-off value for ADC was 0.63 × 10^–3 mm²/s, which yielded an AUC of 0.76. This, in turn, corresponded to a sensitivity, specificity, and accuracy of 84.2%, 59.0%, and 67.2%, respectively. The combined cut-off value of TCL and ADC yielded an AUC of 0.82. The specificity (84.6%) and accuracy (81.0%) of the combined value were superior to their individual values (P < 0.05).Conclusion: A combination of TCL and ADC values provided high specificity and accuracy for detecting EPE of prostatic cancer with CA.     

Precise immunological evaluation rationalizes the design of a self-adjuvanting vaccine composed of glycan antigen,TLR1/2 ligand,and T-helper cell epitope

Sialyl-Tn (STn), overexpressed on various tumors, has been investigated for its application in anti-cancer vaccine therapy. However, Theratope, an STn-based vaccine, failed in the phase III clinical trial due to poor immunogenicity and epitope suppression by the foreign carrier protein. We therefore developed a self-adjuvanting STn based-vaccine, a conjugate of clustered STn (triSTn) antigen, TLR1/2 ligand (Pam₃CSK₄), and T-helper (Th) cell epitope, and found that this three-component self-adjuvanting vaccine effectively resulted in the production of anti-triSTn IgG antibodies. We herein analyzed immune responses induced by this self-adjuvanting vaccine in detail. We newly synthesized two-component vaccines, i.e., Pam₃CSK₄- or Th epitope-conjugated triSTn, as references to evaluate the immune-stimulating functions of Pam₃CSK₄ and Th epitope. Immunological evaluation of the synthesized vaccine candidates revealed that Pam₃CSK₄ was essential for antibody production, indicating that the uptake of triSTn antigen by antigen-presenting cells (APCs) was promoted by the recognition of Pam₃CSK₄ by TLR1/2. The function of the Th epitope was also confirmed. Th cell activation was important for boosting antibody production and IgG subclass switching. Furthermore, flow cytometric analyses of immune cells, including T cells, B cells, dendritic cells, and other monocytes, were first employed in the evaluation of self-adjuvanting vaccines and revealed that the three-component vaccine was able to induce antigen-specific immune responses for efficient antibody production without excessive inflammatory responses. Importantly, the co-administration of Freund''s adjuvants was suggested to cause excessive myeloid cell accumulation and decreased plasma cell differentiation. These results demonstrate that vaccines can be designed to achieve the desired immune responses via the bottom-up construction of each immune element.

Detailed analysis of a three-component self-adjuvanting vaccine revealed that conjugate vaccines can be designed to achieve the desired immune responses via bottom-up construction of the necessary immune elements.     

Addition of Two Substantial Side-Branch Silencers to the Interference Silencer by Incorporating a Zero-Mass Metamaterial

Zero-mass metamaterials comprise an orifice and a thin film. The resonance between the film and the air mass of the orifice hole is caused by sound waves, which significantly decreases the transmission loss at a specific frequency. The study novelly incorporates acoustic metamaterials in the delay tube of an interference silencer. In this case, it is determined that an interference silencer and a “side-branch silencer with two different branch pipe lengths” can be realized in a single silencer. At certain frequencies, the acoustic mass of the acoustic metamaterial approaches zero, which results in an interference silencer with the full length of the delay tube applied. At other frequencies, the acoustic metamaterial acts as a rigid wall with high transmission loss, thereby reflecting sound waves at the zero-mass metamaterial location. In this case, it is a side-branch silencer with two different tube lengths, corresponding to the tube lengths from the entrance and exit of the delay tube to the zero-mass metamaterial, respectively. The incorporation of zero-mass metamaterial into an interference-type silencer can introduce the silencing effect of a side-branch silencer with two different branch tube lengths without increasing the volume of the interference-type silencer. Theoretical values were obtained using the transfer matrix. Consequently, the theoretical and experimental values were close, enabling us to predict the transmission loss of the proposed silencer.     

Metastatic seeding of bile duct carcinoma in the transhepatic catheter tract: Report of a case

We describe herein the case of a 51-year-old woman in whom metastatic tumor seeding of the percutaneous transhepatic biliary drainage tract occurred following a pancreatoduodenectomy for carcinoma of the distal common bile, duct. An abdominal computed tomography scan done 6 months after the initial operation detected a hepatic lesion located at the site of the previous percutaneous transhepatic biliary drainage tract. Implantation of bile duct carcinoma in the drainage tract was diagnosed, and the recurrent tumor was successfully resected by performing a subsegmentectomy of segment 3 and removal of the adjacent abdominal wall. At present, 5 years and 4 months after the second resection, the patient is in good health without any signs of recurrence. This case report demonstrates that an aggressive surgical approach should be performed for tumor seeding of a transhepatic biliary catheter tract.     

Oxygen pressure measurement during grip exercise reveals exercise intolerance after radial harvest

BACKGROUND: Exercise intolerance of the hand after harvest of the radial artery is not well understood, although mild reductions of blood flow to the hand are reported. To ascertain its prevalence, patient symptoms implying potential exercise intolerance were evaluated by measuring transcutaneous oxygen pressure of the hand during grip exercise. For ascertaining predictive values, we verified ulnar flow reserve measured by Doppler ultrasonography before the harvest of radial artery. METHODS: Forty patients whose radial artery was harvested for coronary bypass graft, were interviewed and tested 1 year after operation, and their preoperative ultrasonographic data compared. RESULTS: Five patients (12.5%) had mild symptoms implying exercise intolerance. Exercise tests revealed severe decreases in tissue oxygenation in 7 patients (17.5%), but in accordance with symptoms (p = 0.0018). Tissue oxygenation in the operated hand was lower than in the nonoperated even in asymptomatic patients (p = 0.0011). Preoperative Doppler echography revealed that ulnar arteries of symptomatic patients were smaller (p = 0.0019) and carried lower blood flows during manual compression of the radial artery (p = 0.0004) compared with those of asymptomatic patients. Smaller ulnar arteries (less than 1.4 mm/m(2)) with poor flow reserves (less than 60 mL x min(-1) x m(-2) during radial compression) appear to indicate risks for exercise intolerance (p = 0.0004). CONCLUSIONS: More than 10% of patients after harvest of radial arteries had mild symptoms implying exercise-intolerance, which accorded with abnormal tissue oxygenation during grip exercise. Work habits of patients should be considered in radial harvest decisions, especially if preoperative Doppler echography indicates lower flow reserves for the ulnar artery.     

Operated hepatocellular carcinoma in two HIV- and HCV-positive hemophilic patients

Some hemophilic patients in Japan suffer from infections with both human immunodeficiency virus (HIV) and hepatitis virus because they received contaminated nonheated blood products. Coinfection with HIV appears to accelerate the course of chronic hepatitis. Although powerful antiviral therapy was introduced as HIV treatment and the prognosis of HIV patients was dramatically improved, the risk of rapid progression of hepatitis and carcinogenesis remains for the patients. Recently, we performed surgery for hepatocellular carcinoma (HCC) in two hemophilic patients with HIV and hepatitis C virus (HCV) coinfection. Case 1 was a 52-years-old man who suffered from liver cirrhosis, hypersplenism, and hyperammonemia due to portosystemic shunt. A recent abdominal computed tomography (CT) scan had revealed a low-density area in segment VI of the liver. Splenectomy and partial resection of the liver were performed. Case 2 was a 66-year-old man who had been diagnosed with chronic hepatitis at age 50, and HIV infection at age 52 years. When his serum alpha-fetoprotein level was increased, CT scan of the liver revealed a mass in segment VIII. Subsegmentectmy of the liver was performed. Although the CD4 value in each patient was lower than 200µl, the operations were safely carried out and no major complication occurred. Because the chance of encountering HCC patients infected with HIV and HCV is increasing in Japan, we should consider the perioperative care of these patients, as well as the protection of medical workers against HIV infection.     

Transcatheter embolization of an aortobronchial fistula with N-butyl cyanoacrylate

Aortobronchial fistula is a fatal complication after thoracic aortic surgery. So far, treatment options for aortobronchial fistula have included surgical and endovascular stent-graft methods. Herein, a case of an aortobronchial fistula with life-threatening hemoptysis managed with transcatheter embolization of the fistula with N-butyl cyanoacrylate is reported. For the patient with an aortobronchial fistula who cannot be treated by surgical or endovascular stent-graft methods, transcatheter embolization of the fistula may be the only available life-saving method.