Initial experience with the transanal approach for lateral pelvic lymph node dissection in rectal cancer.

BACKGROUND: The efficacy and safety of transanal lateral pelvic lymph node dissection (TaLPLND) in rectal cancer has not yet been clarified. The aim of the present study was to evaluate the short-term results as an initial experience of TaLPLND. METHODS: This retrospective study included patients with middle to lower rectal cancer who underwent TaLPLND from July 2018 to July 2021. Our institutions targeted lymph nodes in the internal iliac area and the obturator area for lateral pelvic lymph node dissection (LPLND). RESULTS: A total of 30 consecutive patients with rectal cancer were included in this analysis. The median age was 60 years (range, 36-83 years), and the male-female ratio was 2:1. The median operative time was 362 min (IQR, 283-661 min), and the median intraoperative blood loss was 74 ml (IQR, 5-500 ml). Intraoperative blood transfusion was required in one case. No cases required conversion to laparotomy. TaLPLND was performed bilaterally in 13 patients (43.3%). Five patients (16.7%) underwent LPLND with combined resection of the internal iliac vessels. The median distance of the distal margin from the anal verge was 20 mm. The pathological radial margin (pRM) was positive in one case, and the negative pRM rate was 96.7%. Short-term postoperative complications (Clavien-Dindo classification grade ≥ II) were observed in nine cases (30.0%). There were no cases of reoperation or mortality. The median number of harvested lateral pelvic lymph nodes was 11 (range, 3-28). On pathological examination, lateral pelvic lymph nodes were positive for metastasis in seven cases (23.3%). CONCLUSIONS: TaLPLND appeared to be beneficial from an oncological point of view because it was close to the upstream lymphatic drainage from the tumor. The short-term outcomes of this initial experience indicate that this novel approach is feasible.

Assessment of Heating on Titanium Alloy Cerebral Aneurysm Clips during 7T MRI.

BACKGROUND AND PURPOSE: Patients with cerebral aneurysms often undergo MR imaging after microsurgical clipping. Ultra-high-field MR imaging at 7T may provide high diagnostic capability in such clinical situations. However, titanium alloy clips have safety issues such as adverse interactions with static magnetic fields and radiofrequency-induced heating during 7T MR imaging. The purpose of this study was to quantitatively assess temperature increases on various types of titanium alloy aneurysm clips during 7T MR imaging. MATERIALS AND METHODS: Five types of titanium alloy aneurysm clips were tested, including combinations of short, long, straight, angled, and fenestrated types. Each clip was set in a phantom filled with gelled saline mixed with polyacrylic acid and underwent 7T MR imaging with 3D T1WI with a spoiled gradient recalled acquisition in the steady-state technique. Temperature was chronologically measured at the tips of the clip blade and head, angled part of the clip, and 5 mm from the tip of the clip head using MR imaging-compatible fiber-optic thermometers. RESULTS: Temperature increases at all locations for right-angled and short straight clips were <1°C. Temperature increases at the angled part for the 45° angled clip and the tip of the clip head for the straight fenestrated clip were >1°C. Temperature increases at all locations for the long straight clip were >2°C. CONCLUSIONS: Temperature increases on the right-angled and short straight clips remained below the regulatory limit during 7T MR imaging, but temperature increases on the 45° angled, straight fenestrated, and long straight clips exceeded this limit.

A PHANTOM STUDY TO DETERMINE THE OPTIMAL PLACEMENT OF EYE DOSEMETERS ON INTERVENTIONAL CARDIOLOGY STAFF.

The International Commission on Radiological Protection has substantially reduced the recommended maximum annual eye lens dose for workers. Use of a dedicated eye dosemeter is one method for accurate dose monitoring. The main aim of this study was to yield recommendations for optimal placement of eye dosemeters to estimate the eye dose to interventional cardiology physicians and nurses. A phantom measurement was conducted to simulate typical interventional cardiology procedures. Considering eight X-ray tube angulations, the left side of the head position provide good estimates for physician, and the forehead position provide good estimates for nurse.

Survey of volume CT dose index in Japan in 2014.

OBJECTIVE: The aims of this study are to propose a new set of Japanese diagnostic reference levels (DRLs) for 2014 and to study the impact of tube voltage and the type of reconstruction algorithm on patient doses. The volume CT dose index (CTDI(vol)) for adult and paediatric patients is assessed and compared with the results of a 2011 national survey and data from other countries. METHODS: Scanning procedures for the head (non-helical and helical), chest and upper abdomen were examined for adults and 5-year-old children. A questionnaire concerning the following items was sent to 3000 facilities: tube voltage, use of reconstruction algorithms and displayed CTDI(vol). RESULTS: The mean CTDI(vol) values for paediatric examinations using voltages ranging from 80 to 100 kV were significantly lower than those for paediatric examinations using 120 kV. For adult examinations, the use of iterative reconstruction algorithms significantly reduced the mean CTDI(vol) values compared with the use of filtered back projection. Paediatric chest and abdominal scans showed slightly higher mean CTDI(vol) values in 2014 than in 2011. The proposed DRLs for adult head and abdominal scans were higher than those reported in other countries. CONCLUSION: The results imply that further optimization of CT examination protocols is required for adult head and abdominal scans as well as paediatric chest and abdominal scans. ADVANCES IN KNOWLEDGE: Low-tube-voltage CT may be useful for reducing radiation doses in paediatric patients. The mean CTDI(vol) values for paediatric scans showed little difference that could be attributed to the choice of reconstruction algorithm.

Indoleamine 2,3-dioxygenase in the pathogenesis of tuberculous pleurisy.

BACKGROUND: Pleural fluid is a frequent manifestation in pulmonary diseases, such as lung cancer and infectious diseases, including pulmonary tuberculosis (TB). The enzyme indoleamine 2,3-dioxygenase (IDO) catalyses tryptophan through the kynurenine pathway, and is considered a crucial immunoregulatory molecule mediating immune tolerance. Recent studies have shown IDO activity to be a novel prognostic factor not only in cancer patients but also in those with infectious diseases, including pneumonia and pulmonary TB. However, no studies have measured and determined the clinical significance of IDO activity in pleural fluid. METHODS: We enrolled 92 patients, including 34 with tuberculous pleurisy (TBP), 36 with malignant pleuritis and 15 with parapneumonic effusions. IDO activity was evaluated using liquid chromatography/electrospray ionisation tandem mass spectrometry, and was estimated by calculating kynurenine-to-tryptophan ratio. RESULTS: Pleural fluid from patients with TBP had significantly higher kynurenine concentrations and significantly lower tryptophan concentrations, resulting in significantly higher IDO activity compared with pleural effusion or serum from non-tuberculous pleuritis (all P < 0.001). Pleural tissue from TBP showed enhanced IDO expression in epithelioid granuloma regions by immunohistochemistry. CONCLUSIONS: These results suggest that IDO is strongly involved in the pathogenesis of TBP.

Chronological effects of rifampicin discontinuation on cytochrome P450 activity in healthy Japanese volunteers, using the cocktail method.

Cytochrome P450 (CYP) 1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A are major factors involved in the metabolism of clinically prescribed drugs. Because the time course after drug treatment discontinuation has received little attention, we aimed to clarify the chronological changes of rifampicin-induced CYP enzyme activities after rifampicin discontinuation. Thirteen volunteers took 450 mg of rifampicin once daily, and the cocktail method, which uses caffeine, losartan, omeprazole, dextromethorphan, and midazolam as CYP-specific probes, was repeatedly used for the evaluation of CYP levels. Concentrations of probes and metabolites were determined by liquid chromatography-tandem mass spectrometry. Seven-day rifampicin administration increased CYP2C19 and CYP3A enzyme activities. The induced CYP2C19 and CYP3A activities remained elevated at 4 days after rifampicin discontinuation and returned to baseline levels 8 days after rifampicin discontinuation. CYP1A2 and CYP2D6 enzyme activities showed no significant changes, and CYP2C9 enzyme activity was increased with rifampicin administration, with a tendency toward statistical significance. Drug interactions can occur even after rifampicin discontinuation.

Immunogenicity of dormancy-related antigens in individuals infected with Mycobacterium tuberculosis in Japan.

SETTING: DosR regulon genes are considered essential for Mycobacterium tuberculosis dormancy, and their products are demonstrated to have immunogenicity in M. tuberculosis-infected individuals, suggesting that DosR regulon-encoded proteins are suitable targets for vaccines to control the reactivation of dormant M. tuberculosis. OBJECTIVE: Prospective analysis of T-cell and antibody responses against DosR regulon-encoded antigens in M. tuberculosis-infected individuals in Japan to identify effective vaccine targets. DESIGN: T-cell responses against 33 DosR regulon-encoded antigens were investigated in 26 consecutive M. tuberculosis-infected individuals--14 with latent tuberculosis infection (LTBI) and 12 with active pulmonary tuberculosis (PTB)--using enzyme-linked immunosorbent spot assay, and antibody responses in 42 consecutive individuals, 14 with LTBI and 28 with PTB. RESULT: Six antigens (Rv0570, Rv1996, Rv2004c, Rv2028c, Rv2029c and Rv3133c) induced stronger T-cell responses in LTBI than in PTB, In contrast, antigen-specific antibody responses to five antigens (Rv0080, Rv1738, Rv2007c, Rv2031c and Rv2032) were found to be stronger in PTB than in LTBI cases. CONCLUSION: T-cell responses to six antigens might contribute to natural protection against dormant M. tuberculosis. These antigens are therefore considered to be potential targets of novel vaccines to control M. tuberculosis reactivation in the Japanese population.

Respiratory mechanics and peripheral airway inflammation and dysfunction in asthma.

BACKGROUND: Clinical application of the forced oscillation technique (FOT) has progressed with the spread of commercially available FOT devices. The correlation between respiratory impedance and spirometry has been reported; however, the association with airway inflammation and pulmonary function, in the lung periphery in particular, is unclear. OBJECTIVE: To assess whether respiratory impedance is associated with peripheral airway inflammation and dysfunction in asthma. METHODS: Subjects included 78 patients with overall controlled asthma. We measured whole-breath or within-breath respiratory system resistance (Rrs) and reactance (Xrs) using a commercially available multi-frequency FOT device (MostGraph-01), and assessed the correlation with the fraction of exhaled nitric oxide (FeNO), alveolar nitric oxide concentration (CANO), maximal NO flux in the conductive airways (J'awNO), and the N2 phase III slope of single breath N2 washout (delta N2 ). RESULTS: The differences between inspiratory and expiratory phases of Xrs at 5 Hz (X5), resonant frequency (Fres), and a low-frequency reactance area (ALX) were significantly correlated with CANO; however, there was no correlation between respiratory impedance and FeNO or J'awNO. The delta N2 values were significantly correlated with whole-breath, inspiratory, and expiratory Rrs and Xrs, except for R20. CONCLUSIONS AND CLINICAL RELEVANCE: We conclude that respiratory impedance reflects peripheral airway inflammation and ventilation inhomogeneity.

Assessment of serum KL-6 as a prognostic marker in pulmonary tuberculosis patients.

Although serum Krebs von den Lungen-6 (KL-6) levels are reported to increase in pulmonary tuberculosis (PTB) patients according to disease activity, the relationship between serum KL-6 levels and prognosis remains unclear. In this study, we prospectively examined serum KL-6 levels in 188 PTB patients and assessed 60-day mortality. Univariate and multivariate logistic regression analysis demonstrated that serum KL-6 levels were not significantly associated with prognosis. For receiver operating characteristic analysis, the area under the curve had low accuracy for predicting mortality. These findings indicate that serum KL-6 levels do not perform adequately for use as a prognostic marker in patients with PTB.

Drug lymphocyte stimulation test is not useful for side effects of anti-tuberculosis drugs despite its timing.

BACKGROUND: Some patients have adverse reactions to anti-tuberculosis drugs. We have reported that drug lymphocyte stimulation testing (DLST), which we performed at Week 1 of adverse reactions, provides little useful information (14.9% sensitivity). However, it remains unclear whether the time of performance of the DLST contributed to these results. METHODS: Patients with adverse reactions to anti-tuberculosis drugs, including rash, hepatitis and fever, underwent DLST in the first week of the adverse reaction and were then randomly assigned to Group A (among whom a second DLST was performed 2 months after the reaction) or Group B (among whom a second DLST was performed >12 months after the reaction). We compared Group A with Group B to determine the optimal timing for the performance of DLST. The causative drug was identified by an oral drug provocation test. RESULTS: Consistent with the previous study, the sensitivity of DLST performed in the first week was low (14.3%). For DLST performed later, the sensitivity in Group A and Group B was respectively 5.0% and 6.7%. CONCLUSIONS: DLST is not useful for determining the causative drug in patients with rash, hepatitis or fever reactions to anti-tuberculosis drugs, regardless of when it is performed.

Pulmonary dendritic cell accumulation in usual interstitial pneumonia and nonspecific interstitial pneumonia.

BACKGROUND: Pulmonary dendritic cells (DCs) are key regulators of immune responses. An increased accumulation of DCs was reported in the lungs of patients with idiopathic interstitial pneumonia (IIP). OBJECTIVE: This study aimed to investigate the number of pulmonary DCs in patients with collagen vascular disease associated interstitial lung diseases (CVD-ILDs). DESIGN: Lung tissue samples obtained from 27 patients with IIP and 39 patients with CVD-ILD were detected using monoclonal antibodies against CD1a, CD1c, CD83, Langerin and DC-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN). RESULTS: No significant differences in the number or distribution of DCs were observed between patients with IIP and CVD-ILDs. When DC marker expression was analyzed according to pathological subgroup, patients with idiopathic usual interstitial pneumonia (UIP) showed increased DC-SIGN staining when compared with CVD-UIP (p < 0.05). CONCLUSION: Both mature and immature DCs accumulate in CVD-ILDs. The number of DCs expressing DC-SIGN in CVD-UIP was decreased compared with that in idiopathic UIP. The variation in accumulated DC-SIGN-positive cells might help to explain the differences in the development and maintenance of lung inflammation between idiopathic UIP and CVD-UIP.

PKCη promotes a proliferation to differentiation switch in keratinocytes via upregulation of p27Kip1 mRNA through suppression of JNK/c-Jun signaling under stress conditions.

To maintain epidermal homeostasis, the balance between keratinocyte proliferation and differentiation is tightly controlled. However, the molecular mechanisms underlying this balance remain unclear. In 3D organotypic coculture with mouse keratinocytes and fibroblasts, the thickness of stratified cell layers was prolonged, and growth arrest and terminal differentiation were delayed when PKCη-null keratinocytes were used. Re-expression of PKCη in PKCη-null keratinocytes restored stratified cell layer thickness, growth arrest and terminal differentiation. We show that in 3D cocultured PKCη-null keratinocytes, p27(Kip1) mRNA was downregulated, whereas JNK/c-Jun signaling was enhanced. Furthermore, inhibition of JNK/c-Jun signaling in PKCη-null keratinocytes led to upregulation of p27(Kip1) mRNA, and to thinner stratified cell layers. Collectively, our findings indicate that PKCη upregulates p27(Kip1) mRNA through suppression of JNK/c-Jun signaling. This results in promoting a proliferation to differentiation switch in keratinocytes.

Usefulness of serum procalcitonin levels in pulmonary tuberculosis.

There are very few data on serum procalcitonin (PCT) levels in pulmonary tuberculosis (PTB) patients who are negative for HIV. We assessed serum PCT in consecutive patients diagnosed with pulmonary tuberculosis or community-acquired pneumonia (CAP) on admission to discriminate between PTB and CAP, and examined the value of prognostic factors in PTB. 102 PTB patients, 62 CAP patients, and 34 healthy volunteers were enrolled. Serum PCT in PTB patients was significantly lower than in CAP patients (mean ± sd 0.21 ± 0.49 versus 4.10 ± 8.68 ng·mL⁻¹; p < 0.0001). By receiver-operating characteristic curve analysis, serum PCT was an appropriate discrimination marker for PTB and CAP (area under the curve 0.866). PTB patients with ≥ 0.5 ng·mL⁻¹ (normal cut-off) had significantly shorter survival than those with < 0.5 ng·mL⁻¹ (p < 0.0001). Serum PCT is not habitually elevated in HIV-negative PTB patients and is a useful biomarker for discriminating between PTB and CAP; however, when serum PCT is outside the normal range, it is a poor prognostic marker.

Induction of Th1 immune responses to Japanese cedar pollen allergen (Cry j 1) in mice immunized with Cry j 1 conjugated with CpG oligodeoxynucleotide.

We determined whether a major Japanese cedar pollen allergen (Cry j 1) conjugated with CpG oligodeoxynucleotide would enhance allergen-specific Th1 responses in mice. Cry j 1 conjugated with CpG (Cry j 1-CpG) induced IL-12 in the spleen cells of naïve mice. Cry j 1-CpG immunization of BALB/c mice suppressed anti-Cry j 1 IgE response and enhanced anti-Cry j 1 IgG(2a) to subsequent Cry j 1 and alum adjuvant injection. CD4(+)T cells isolated from the spleens in mice immunized with Cry j 1-CpG produced higher IFN-γ levels than did CD4(+)T cells obtained from mice as negative controls. Our results suggested that Cry j 1-CpG immunization can induce Cry j 1-specific Th1 immune responses, thereby inhibiting IgE response to the pollen allergen.

[Patient skin injury in cardiac intervention procedures].

PURPOSE: To discuss the circumstances of patient skin injury in cardiac interventional radiology (IVR). To demonstrate the importance of evaluating the patient radiation dose in IVR. To show the need for the appropriate patient follow-up after IVR to identify radiation effects. To highlight the incidence of skin injuries during IVRs. CONTENT ORGANIZATION: Evaluation of 400 consecutive percutaneous coronary interventions (PCIs). The radiation dose, number of cine runs, and fluoroscopic time were recorded for all patients. The skin on the patients' backs was reviewed periodically after PCI to identify radiation injury. The relationships between patient skin effects and factors such as the radiation dose were investigated. Reviewing previous reports of patient radiation injury occurrence rate, fluoroscopic time, radiation dose (if available), etc. SUMMARY: Although increasing numbers of case reports of patient radiation injury resulting from IVR are being published, these reports likely represent a small fraction of actual cases. Radiation skin injury in IVR is overlooked clinically in many patients. Patients who receive a high radiation dose while undergoing IVR should be followed to identify radiation skin effects, and physicians should seek to establish whether a patient has had previous IVR, together with the entrance site and radiation dose.

High lipoprotein(a) level promotes both coronary atherosclerosis and myocardial infarction: a path analysis using a large number of autopsy cases.

OBJECTIVE: To investigate whether hyper-lipoproteinaemia(a) (Lp(a)) promotes coronary atherosclerosis, acute thrombosis resulting in myocardial infarction (MI), or both. DESIGN: Retrospective chart review. SETTING: A community-based general geriatric hospital. PATIENTS: 1062 consecutive autopsy cases (609 men, 453 women). The mean age at the time of death was 80 years. MAIN OUTCOME MEASURES: A semiquantitative evaluation of the coronary stenosis on cut sections and pathological definition of MI. Lp(a) levels of fresh serum taken antemortem, measured by a latex-enhanced turbidimetric immunoassay. RESULTS: The prevalence of severe coronary stenosis and pathological MI increased linearly with increasing Lp(a) levels with no apparent threshold. The odds ratios (95% CI) of hyper-Lp(a) (2.99 (1.70 to 5.28) for 200-299 mg/l and 3.25 (1.90 to 5.54) for >300 mg/l) for severe coronary stenosis were larger than those of hypertension (2.61 (1.88 to 3.63)), diabetes mellitus (2.09 (1.41 to 3.11)) and hypercholesterolaemia (2.05 (1.31 to 3.21)). The severe coronary sclerosis was much stronger risk of MI (6.28 (4.33 to 9.11)) than hyper-Lp(a), hypertension and diabetes mellitus. A path analysis showed that the Lp(a) levels affected both coronary sclerosis and MI, with path coefficients of 0.15 and 0.07 (direct effect), respectively. In cases with severe coronary sclerosis Lp(a) affected only MI (0.15). CONCLUSIONS: Lp(a) levels have distinct effects on coronary sclerosis and MI, with about half of the overall effect on MI being via coronary sclerosis. This result supports the prothrombotic and a probable proinflammatory role of Lp(a) in coronary events.

Evaluation of patient radiation dose during cardiac interventional procedures: what is the most effective method?

Cardiac interventional radiology has lower risks than surgical procedures. This is despite the fact that radiation doses from cardiac intervention procedures are the highest of any commonly performed general X-ray examination. Maximum radiation skin doses (MSDs) should be determined to avoid radiation-associated skin injuries in patients undergoing cardiac intervention procedures. However, real-time evaluation of MSD is unavailable for many cardiac intervention procedures. This review describes methods of determining MSD during cardiac intervention procedures. Currently, in most cardiac intervention procedures, real-time measuring of MSD is not feasible. Thus, we recommend that physicians record the patient's total entrance skin dose, such as the dose at the interventional reference point when it can be monitored, in order to estimate MSD in intervention procedures.

Effect of radiation monitoring method and formula differences on estimated physician dose during percutaneous coronary intervention.

BACKGROUND: Currently, one or two dosimeters are used to monitor radiation exposure in most cardiac laboratories. In addition, several different formulas are used to convert exposure data into an effective dose (ED). PURPOSE: To clarify the effect of monitoring methods and formula selection on the estimated ED for physicians during percutaneous coronary interventions (PCIs). MATERIAL AND METHODS: The ED of physicians during cardiac catheterization was determined using an optically stimulated luminescence dosimeter (Luxel badge). Two Luxel badges were worn: one beneath a personal lead apron (0.35-mm lead equivalent) at the chest and one outside of the apron at the neck. RESULTS: The difference in the average ED of seven physicians was approximately fivefold (range 1.13-5.43 mSv/year) using the six different formulas in the clinical evaluation. The estimated physician ED differed markedly according to both the monitoring method and formula selected. CONCLUSION: ED estimation is dependent on both the monitoring method and the formula used. Therefore, it is important that comparisons among laboratories are based on the same monitoring method and same formula for calculating the ED.

Simple assessment of cerebral hemodynamics using single-slab 3D time-of-flight MR angiography in patients with cervical internal carotid artery steno-occlusive diseases: comparison with quantitative perfusion single-photon emission CT.

BACKGROUND AND PURPOSE: Visualization of the peripheral arteries on single-slab 3D time-of-flight (TOF) MR angiography (MRA) can reflect blood flow velocity. The velocity in the middle cerebral artery (MCA) may correlate with cerebrovascular reactivity (CVR) to acetazolamide, which can be used to assess hemodynamic impairment. The goal of this study was to compare the signal intensity of the MCA on MRA versus CVR quantified by perfusion single-photon emission CT (SPECT). MATERIALS AND METHODS: The signal intensity of the MCA on single-slab 3D time-of-flight MRA was graded according to the ability to visualize the MCA in 108 cerebral hemispheres of 87 patients with unilateral or bilateral cervical internal carotid artery (ICA) steno-occlusive diseases. SPECT-CVR was also calculated by measuring cerebral blood flow before and after acetazolamide challenge. Ten healthy subjects were studied to obtain control SPECT-CVR values. All subjects provided written informed consent before the study. RESULTS: CVR was significantly lower in cerebral hemispheres with reduced MCA signal intensity than in those with normal intensity (P < .05). When the reduced signal intensity of the MCA on MRA was defined as abnormal, and when a CVR less than the mean--2 SD of healthy subjects was defined as reduced, MRA grading resulted in a 86.2% sensitivity and 69.6% specificity, with 51.0% positive-predictive and 93.2% negative-predictive values to detect reduced CVR. CONCLUSIONS: This simple MRA method can assess hemodynamic impairment with a high negative-predictive value.

Mycobacterium avium complex disease: prognostic implication of high-resolution computed tomography findings.

To evaluate the prognostic implications of computed tomography (CT) findings in assessing responses to treatment in Mycobacterium avium complex (MAC) pulmonary disease without underlying lung disease, high-resolution (HR)CT findings were correlated based on the results of sputum conversion after anti-MAC therapy. A total of 59 patients underwent HRCT before treatment and the therapeutic efficacy was evaluated by the results of sputum conversion. Atelectasis, cavities and pleural thickening on HRCT were significantly more frequent and extensive among patients in the sputum nonconverted group than among those in the converted group. Furthermore, bronchiectasis was also significantly more extensive among patients in the nonconverted group, even though there was no significant difference in frequency between these two groups. These results suggest that high-resolution computed tomography findings are good predictors of response to treatment in Mycobacterium avium complex pulmonary disease.