Prognostic markers including immune and inflammatory factors predict outcomes in patients receiving postoperative radiation therapy for cholangiocarcinoma.

PURPOSE: This study aimed to analyze treatment outcomes and prognostic markers, including immune and inflammatory factors, of postoperative radiation therapy (RT) administered to patients with cholangiocarcinoma (CCA). METHODS: We retrospectively included 59 patients with CCA who underwent surgery and postoperative RT with curative intent from 2004 to 2019. Patients received external irradiation (50 Gy in 25 fractions) using three-dimensional RT. We analyzed prognostic factors of inflammation, such as pre-RT platelet count, hemoglobin, lymphocyte count ratio (LCR) of the leukocyte count, platelet-to-lymphocyte ratio (PLR), and neutrophil-to-lymphocyte ratio (NLR). RESULTS: Tumor stages were distributed as follows: I (n = 8), II (n = 25), III (n = 15), and IVA (n = 11). The median follow-up was 24 months. Two-year overall survival (OS), cause-specific survival (CSS), progression-free survival (PFS), and locoregional control (LRC) rates were 59.5%, 62.0%, 40.1%, and 66.7%, respectively. Univariate analysis revealed that lower LCR was significantly associated with shorter PFS (p = 0.0446). There was no significant difference between the median baseline values of PLR and NLR; and age ≥75, positive regional lymph node metastases (N+), and chemotherapy after RT were significantly associated with poor OS. Multivariate analysis revealed a significant association of N+ with worse OS, PFS, and CSS and that lower LCR was significantly associated with better PFS (p = 0.0234). Among late toxicity events, two patients (3.38%) were suspected with therapy-related liver toxicity. CONCLUSIONS: Lower LCR before RT was a better prognostic factor for postoperative RT of patients with CCA.

Green fluorescent cAMP indicator of high speed and specificity suitable for neuronal live-cell imaging.

Cyclic adenosine monophosphate (cAMP) is a canonical intracellular messenger playing diverse roles in cell functions. In neurons, cAMP promotes axonal growth during early development, and mediates sensory transduction and synaptic plasticity after maturation. The molecular cascades of cAMP are well documented, but its spatiotemporal profiles associated with neuronal functions remain hidden. Hence, we developed a genetically encoded cAMP indicator based on a bacterial cAMP-binding protein. This indicator "gCarvi" monitors [cAMP]i at 0.2 to 20 µM with a subsecond time resolution and a high specificity over cyclic guanosine monophosphate (cGMP). gCarvi can be converted to a ratiometric probe for [cAMP]i quantification and its expression can be specifically targeted to various subcellular compartments. Monomeric gCarvi also enables simultaneous multisignal monitoring in combination with other indicators. As a proof of concept, simultaneous cAMP/Ca2+ imaging in hippocampal neurons revealed a tight linkage of cAMP to Ca2+ signals. In cerebellar presynaptic boutons, forskolin induced nonuniform cAMP elevations among boutons, which positively correlated with subsequent increases in the size of the recycling pool of synaptic vesicles assayed using FM dye. Thus, the cAMP domain in presynaptic boutons is an important determinant of the synaptic strength.

A randomized trial evaluating the safety profile of sugammadex in high surgical risk ASA physical class 3 or 4 participants.

BACKGROUND: The aim of this randomized, double-blind trial was to evaluate the safety and tolerability profile, including cardiac safety, of sugammadex-mediated recovery from neuromuscular block in participants undergoing surgery who met the American Society of Anesthesiologists (ASA) Physical Class 3 or 4 criteria. Specifically, this study assessed the impact of sugammadex on cardiac adverse events (AEs) and other prespecified AEs of clinical interest. METHODS: Participants meeting ASA Class 3 and 4 criteria were stratified by ASA Class and NMBA (rocuronium or vecuronium) then randomized to one of the following: 1) Moderate neuromuscular block, sugammadex 2 mg/kg; 2) Moderate neuromuscular block, neostigmine and glycopyrrolate (neostigmine/glycopyrrolate); 3) Deep neuromuscular block, sugammadex 4 mg/kg; 4) Deep neuromuscular block, sugammadex 16 mg/kg (rocuronium only). Primary endpoints included incidences of treatment-emergent (TE) sinus bradycardia, TE sinus tachycardia and other TE cardiac arrhythmias. RESULTS: Of 344 participants randomized, 331 received treatment (61% male, BMI 28.5 ± 5.3 kg/m2, age 69 ± 11 years). Incidence of TE sinus bradycardia was significantly lower in the sugammadex 2 mg/kg group vs neostigmine/glycopyrrolate. The incidence of TE sinus tachycardia was significantly lower in the sugammadex 2 and 4 mg/kg groups vs neostigmine/glycopyrrolate. No significant differences in other TE cardiac arrythmias were seen between sugammadex groups and neostigmine/glycopyrrolate. There were no cases of adjudicated anaphylaxis or hypersensitivity reactions in this study. CONCLUSIONS: Compared with neostigmine/glycopyrrolate, incidence of TE sinus bradycardia was significantly lower with sugammadex 2 mg/kg and incidence of TE sinus tachycardia was significantly lower with sugammadex 2 mg/kg and 4 mg/kg. These results support the safety of sugammadex for reversing rocuronium- or vecuronium-induced moderate and deep neuromuscular block in ASA Class 3 or 4 participants. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03346057 .

Outcome of Radiation Therapy for Stage IVB Uterine Cervical Cancer With Distant Lymph Nodes Metastases; Sequential Irradiation for Distant Lymph Nodes Metastases.

BACKGROUND/AIM: This study aimed to evaluate the outcome of radiation therapy for patients with distant lymph node (LN) metastases, without organ metastases from uterine cervical cancer (UCC). PATIENTS AND METHODS: Twenty-six patients with UCC with distant LN metastases received radiotherapy and were retrospectively analyzed. The sites of distant LN metastasis were as follows; Supraclavicular in 19, inguinal in nine, axillary in four, and others in three. The mean dose prescribed for these was 50 (range=40-60) Gy. RESULTS: The 2-year overall, cause-specific, and progression-free survival, and local control of primary tumor rates were 51.3%, 51.3%, 46.9%, and 67.9%. In multivariate analysis, performance status ≥1 (p=0.007), para-aortic LN metastases (p=0.001), and lack of high-dose-rate intracavitary brachytherapy (p=0.033) were significantly associated with poor overall survival. Performance status ≥1 (p=0.004), and para-aortic LN metastases (p=0.014) were significantly associated with poor cause-specific survival. CONCLUSION: This study demonstrated favorable local control in patients with UCC with distant LN metastases.

Treatment Outcome of the Combination Therapy of High-dose rate Intracavitary Brachytherapy and Intensity-modulated Radiation Therapy With Central-shielding for Cervical Cancer.

BACKGROUND/AIM: This study aimed to evaluate the clinical outcome of intensity-modulated radiation therapy (IMRT) and high-dose-rate intracavitary brachytherapy (HDR-ICBT) in uterine cervical cancer (UCC). IMRT consisted of whole-pelvic radiation therapy (WPRT) and sequential WPRT with central-shielding (WPRT-CS). PATIENTS AND METHODS: Thirty UCC patients treated with IMRT using TomoTherapy, were retrospectively analyzed. RESULTS: The median dose of WPRT and WPRT-CS was 36 and 14.4 Gy and the median total dose of these was 50 Gy in 25 fractions (Fr). Median HDR-ICBT dose/Fr to Point A was 25 Gy/5 Fr. Median 2 Gy per fraction-equivalent dose (EQD2) of combined WPRT and HDR-ICBT to Point A (α/ß=10) was 71.0 Gy. The 3-year local control, disease-free survival, and overall survival rates were 89.9%, 83.3%, and 86.3%. CONCLUSION: IMRT of WPRT and WPRT-CS given in combination with HDR-ICBT was a feasible therapy resulting in good disease control and tolerance in patients with UCC.

Impact of superselective intra-arterial and systemic chemoradiotherapy for gingival carcinoma; analysis of treatment outcomes and prognostic factors.

BACKGROUND: We compared outcomes and toxicities between concurrent retrograde super-selective intra-arterial chemoradiotherapy (IACRT) and concurrent systemic chemoradiotherapy (SCRT) for gingival carcinoma (GC). METHODS: We included 84 consecutive patients who were treated for non-metastatic GC ≥ stage III, from 2006 to 2018, in this retrospective analysis (IACRT group: n = 66; SCRT group: n = 18). RESULTS: The median follow-up time was 24 (range: 1-124) months. The median prescribed dose was 60 (6-70.2) Gy (IACRT: 60 Gy; SCRT: 69 Gy). There were significant differences between the two groups in terms of 3-year overall survival (OS; IACRT: 78.8, 95% confidence interval [CI]: 66.0-87.6; SCRT: 50.4, 95% CI: 27.6-73.0; P = 0.039), progression-free survival (PFS; IACRT: 75.6, 95% CI: 62.7-85.2; SCRT: 42.0, 95% CI: 17.7-70.9; P = 0.028) and local control rates (LC; IACRT: 77.2, 95% CI: 64.2-86.4; SCRT: 42.0, 95% CI: 17.7-70.9; P = 0.015). In univariate analysis, age ≥ 65 years, decreased performance status (PS) and SCRT were significantly associated with worse outcomes (P < 0.05). In multivariate analysis, age ≥ 65 years, clinical stage IV, and SCRT were significantly correlated with a poor OS rate (P < 0.05). Patients with poorer PS had a significantly worse PFS rate. Regarding acute toxicity, 22 IACRT patients had grade 4 lymphopenia, and osteoradionecrosis was the most common late toxicity in both groups. CONCLUSIONS: This is the first report to compare outcomes from IACRT and SCRT among patients with GC. ALL therapy related toxicities were manageable. IACRT is an effective and safe treatment for GC.

Outcomes of treatment for localized prostate cancer in a single institution: comparison of radical prostatectomy and radiation therapy by propensity score matching analysis.

OBJECTIVES: To compare the outcomes of radical prostatectomy (RP), intensity-modulated radiation therapy (IMRT), and low-dose-rate brachytherapy (BT) using propensity score matching analysis in patients with clinically localized prostate cancer. METHODS: A group of 2273 patients with clinically localized prostate cancer between January 2004 and December 2015 at the Yokohama City University hospital were identified. The records of 1817 of these patients, who were followed up for a minimum of 2 years, were reviewed; 462 were treated with RP, 319 with IMRT, and 1036 with BT. The patients were categorized according to the National Comprehensive Cancer Network risk classification criteria, and biochemical outcomes and overall survival rates were examined. Biochemical failure for RP was defined as prostate-specific antigen (PSA) levels > 0.2 ng/ml, and for IMRT and BT as nadir PSA level + 2 ng/ml. Propensity scores were calculated using multivariable logistic regression based on covariates, including the patient's age, preoperative PSA, Gleason score, number of positive cores, and clinical T stage. RESULTS: Median follow-up was 77 months for the RP, 54 months for IMRT, and 66 months for BT patients. After the propensity scores were adjusted, a total of 372 (186 each) and 598 (299 each) patients were categorized into RP vs IMRT and RP vs BT groups, respectively. Kaplan-Meier analysis did not show any statistically significant differences in terms of overall survival rate between these groups (RP vs IMRT: p = 0.220; RP vs BT: p = 0.429). IMRT was associated with improved biochemical failure-free survival compared to RP in all risk groups (high-risk: p < 0.001; intermediate-risk: p = 0.009; low-risk: p = 0.001), whereas significant differences were observed only in the intermediate-risk group (p = 0.003) within the RP vs BT group. CONCLUSION: The results of our propensity score analysis of mid-term localized prostate cancer treatment outcomes demonstrated no significant differences in the overall survival rate. Despite the difference in biochemical failure definition between surgery and radiotherapeutic approaches, the results of this study demonstrate improved biochemical control favoring IMRT and BT as compared to RP.

Outcome of Radiation Therapy for Locally Advanced Vulvar Carcinoma: Analysis of Inguinal Lymph Node.

BACKGROUND/AIM: The aim of this study was to define the outcome of radiation therapy for vulvar carcinoma, and to investigate the effectiveness of therapeutic and prophylactic inguinal lymph node (ILN) irradiation. Because reports about the treatment of ILN were limited. PATIENTS AND METHODS: Thirty consecutive vulvar carcinoma patients were treated using external beam radiation therapy (EBRT) for definitive disease (n=25) or postoperatively (n=5). Twenty-four (80%) had squamous cell carcinoma (SCC). Tumor stages (2002 UICC) ranged from 0 to IVB, with no distant metastases. RESULTS: The median total prescribed dose for primary tumor was 64.8 Gy. The 2-year overall survival rate was 25.3%. The outcome was significantly better in patients with ILNs<30 mm (p=0.005) and patients receiving prescribed doses >60 Gy (p=0.002). CONCLUSIONS: ILN diameters ≤30 mm and prescribed doses over 60 Gy were associated with ILN control in patients with vulvar carcinoma.

Radiation Therapy for Uterine Cervical Cancer With Lung Metastases Including Oligometastases.

BACKGROUND/AIM: To investigate the role and outcomes of radiation therapy (RT) for stage IVB uterine cervical cancer (UCC) patients with lung (oligo) metastases due to the lack of recent reports on the subject. PATIENTS AND METHODS: The cohort for this retrospective study comprised 23 consecutive patients with UCC (squamous cell carcinoma, n=13) and lung metastases who had received pelvic RT. Ten had lung metastases only, including 7 with oligometastases (≤4 lung metastases); the remaining 13 also had other distant metastases. RESULTS: Nine (39.1%) of the 22 patients (95.7%) completed RT without interruption. The 1-year primary progression-free rate was 95.2%. The 1-year overall survival rate was 47.2 % (estimated median survival: 9 months). Significant prognostic factors for survival included: i) ≤4 lung metastases (p=0.035), ii) unilateral lung metastases (p=0.039), iii) primary tumor diameter <100 mm (p<0.001), and iv) ECOG performance status <1 (p=0.015). CONCLUSION: RT is safe and effective for stage IVB UCC patients with lung metastases.

Outcome of postoperative radiation therapy for cholangiocarcinoma and analysis of dose-volume histogram of remnant liver.

The aim of this study was to analyze dose-volume histogram (DVH) of the remnant liver for postoperative cholangiocarcinoma (CCA) patients, to find toxicity rates, and to confirm efficacy of postoperative radiation therapy (RT).Thirty-two postoperative CCA patients received partial liver resection and postoperative RT with curative intent. The "liver reduction rate" was calculated by contouring liver volume at computed tomography (CT) just before the surgery and at CT for planning the RT. To evaluate late toxicity, the radiation-induced hepatic toxicity (RIHT) was determined by the common terminology criteria for adverse events toxicity grade of bilirubin, aspartate transaminase, alanine transaminase, alkaline phosphatase, and albumin, and was defined from 3 months after RT until liver metastasis was revealed. The radiation-induced liver disease (RILD) was also evaluated.Tumor stages were distributed as follows: I: 1, II: 8, IIIA: 1, IIIB: 6, IIIC: 14, IVA: 2. Median prescribed total dose was 50 Gy. Median follow-up time was 27 months. Two-year overall survival (OS): 72.4%, disease-free survival: 47.7%, local control: 65.3%, and the median survival time was 40 months. The median "liver reduction rate" was 21%. The OS had statistically significant difference in nodal status (P = .032) and "liver reduction rate" >30% (P = .016). In the association between the ≥grade 2 RIHT and DVH, there were significantly differences in V30 and V40 (P = .041, P = .034), respectively. The grade ≥2 RIHT rates differ also significantly by sex (P = .008). Two patients (6.2%) were suspected of RILD.We suggest that RT for remnant liver should be considered the liver V30, V40 to prevent radiation-induced liver dysfunction.

Acute and late toxicities in localized prostate cancer patients treated with low-dose 125I brachytherapy (110 Gy) in combination with external beam radiation therapy versus brachytherapy alone (160 Gy).

PURPOSE: The aim of this analysis was to compare acute and late toxicities between low-dose-rate brachytherapy (LDR-BT) (110 Gy) in combination with 45 Gy in 25 fractions external beam radiation therapy (EBRT) and LDR-BT (160 Gy) alone for localized prostate cancer. MATERIAL AND METHODS: One hundred five consecutive patients with localized prostate cancer treated from May 2014 to May 2017 were included in this retrospective analysis. Sixty patients received combination therapy and 45 patients received BT monotherapy. The LDR-BT procedure was performed using 125I seeds. RESULTS: The median follow-up time was 28 months in both groups. Three-year effect rates were overall survival: 100% in both groups. The biochemical failure rate was 2.3% in the combination group and 0% in the monotherapy group (p = 0.373). No patients died during the study period. In both groups, almost all the patients experienced acute urethritis. There was a significant difference between the combination therapy group (8.3%) and BT monotherapy group (11.1%) in late genitourinary (GU) toxicities ≥ grade 2 (p = 0.035). Only 2 patients (3.3%) in the combination therapy group developed late ≥ grade 2 rectal hemorrhage. There were no significant differences between two groups in hematuria ≥ grade 2 (p = 0.068) or rectal hemorrhage ≥ grade 2 (p = 0.206). CONCLUSIONS: To our knowledge, this is the first report to compare the GU and gastrointestinal toxicities between the combination therapy and BT monotherapy (160 Gy) for localized prostate cancer. Unexpectedly, there were more late GU toxicities (except for hematuria) in the BT monotherapy group.

Treatment outcome for locally advanced non-small-cell lung cancer using TomoDirect plan and its characteristics compared to the TomoHelical plan.

INTRODUCTION: TomoDirect (TD) is an intensity-modulated radiotherapy system that uses a fixed gantry angle instead of the rotational beam delivery used in the TomoHelical (TH) system. This study was performed (1) to evaluate the treatment outcome of the TD plan for locally advanced non-small-cell lung cancer (NSCLC) and (2) to compare the characteristics of TD plans with those of TH plans. METHODS: Twenty-one patients with NSCLC were treated using the TD system. The prescribed dose was 40 Gy/20 Fx for the initial planning target volume (PTV), which included the gross tumour volume (GTV) and lymph node regions. A boost plan of 20 Gy/10 Fx was then applied, focusing on the GTV. For the planning study, matched TH plans of 40 Gy for the initial PTV were created for each patient, to meet the same dosimetric constraints specified in the TD plans. RESULTS: The 2-year overall survival, progression-free survival and local control rates were 47%, 45% and 74% respectively. Grade 2 treatment-related pneumonitis occurred in three (14%) patients. The planning study comparing TD and TH showed that dose distribution to GTV and PTV were not significantly different. The lung V5 Gy was lower in the TD plans than TH plans (46.4 ± 5.4 vs. 52.3 ± 8.5), while the V20 Gy was higher (26.2 ± 4 vs. 24 ± 4.3). The TD plans had a significantly shorter treatment time than TH plans (4.5 ± 1.3 min vs. 9.8 ± 1.5 min). CONCLUSIONS: TD is a clinically acceptable treatment option for NSCSL. The quality of the TD and TH plans are comparable.

Radiation Therapy for Patients with Bone Metastasis from Uterine Cervical Cancer: Its Role and Optimal Radiation Regimen for Palliative Care.

AIM: To determine the role of radiation therapy for patients with bone metastasis from uterine cervical cancer and identify an optimal radiation regimen. PATIENTS AND METHODS: A total of 20 patients with bone metastases from uterine cervical cancer received radiation therapy to the pelvis. The median total dose of 60.2 Gy in the 2 Gy per fraction-equivalent dose (EQD2) was delivered to cervical tumors of all patients. Thirteen patients underwent chemotherapy during and/or following radiation therapy. RESULTS: In 18 of 20 patients, the primary tumors disappeared or were markedly reduced after radiation therapy. In all but one of 17 patients with pelvic pain and bleeding, these symptoms disappeared or were remarkably relieved. However, three patients had primary tumor progression at 7, 9, and 15 months after irradiation with total doses of 56.8, 58.4, and 68.3 Gy in EQD2, respectively. Two of these patients had relapses of bleeding and pain. The primary progression-free rate considering all patients was 69% at 1 year and 34% at 2 years. The corresponding overall survival rates were 34% at 1 year, and 8% at 2 years, with an estimated median survival time of 7 months. The number of metastatic bone sites (p=0.027) and administration of chemotherapy (p<0.001) were significant prognostic factors for survival. CONCLUSION: Radiation therapy is effective for relief of pelvic symptoms in patients with bone metastasis from uterine cervical cancer. For patients who are expected to survive for more than 1 year, almost curative-dose irradiation to primary tumors is recommended.

Local control and intermediate-term cosmetic outcome following IMRT for nasal tumors : An update.

OBJECTIVE: This study aims to evaluate local control and intermediate-term cosmetic outcome in patients with cancer of the nose treated with intensity-modulated radiotherapy (IMRT). METHODS: From June 2008 to September 2015, 36 consecutive patients presenting with nasal cavity, ala of the nose, or nasal vestibule tumors were treated at the Department of Radiation Oncology, University Hospital Zurich either postoperatively (n = 14; 3/14 with nasal ablation) or with definitive IMRT (n = 22). Of these 36 patients, 8 presented with recurrent disease after surgery only and 1/36 with N1 disease. Concurrent systemic therapy was administered in 18/36 patients (50%). Nasal follow-up (FU) imaging documentation of 13 patients with preserved organ and >6 months FU offers a pre/post IMRT FU comparison. In addition, these patients' subjective evaluation of cosmesis was assessed. RESULTS: Mean/median FU was 41/33 months (range 5-92 months). Salvage ablation with curative intent was undergone by 3 patients with local relapse after definitive (n = 2) and postoperative (n = 1) IMRT. The 3­year local control, ultimate local control, and overall survival rates were 90, 97, and 90 %, respectively. Subjective and objective cosmetic outcome after IMRT is very satisfying so far. CONCLUSION: IMRT for nasal tumors was found to be effective and well tolerated. Intermediate-term cosmetic results are good. Radical surgical procedures may be saved for curative salvage treatment.

Radiation therapy for stage IVA uterine cervical cancer: treatment outcomes including prognostic factors and risk of vesicovaginal and rectovaginal fistulas.

PURPOSE: To evaluate the safety and efficacy of radiation therapy for stage IVA uterine cervical cancer and to identify an optimal radiation regimen. RESULTS: Seventeen of the 28 patients developed recurrence after radiation therapy (local recurrence in 10 and distant metastasis in 12). The local control and distant metastasis-free rates at 3 years in all patients were 61% and 49%, respectively. Fourteen patients died after radiation therapy, and all but 2 died of tumor progression. The disease-free, cause-specific, and overall survival rates at 3 years in all patients were 32%, 49%, and 45%, respectively, and the estimated median survival time was 32 months. Tumor size (P = 0.007) and involvement in the lower third of vagina (P = 0.006) were significant prognostic factors for local control. Older age (P = 0.018) and performance status (P = 0.020) were significant prognostic factors for distant metastasis. The presence of hydronephrosis was the sole significant prognostic factor for survival (P = 0.026). Only 2 patients developed grade 3 late toxicities (vesicovaginal fistula and radiation proctitis, respectively). MATERIALS AND METHODS: Twenty-eight patients with stage IVA uterine cervical cancer received radiation therapy. All patients initially received external pelvic irradiation at a median dose of 50.4 Gy in 28 fractions. Twenty patients also received high-dose-rate intracavitary brachytherapy at a median dose of 22 Gy in 4 fractions. These fraction sizes were lower than conventional sizes. The total median dose for all 28 patients was 68.7 Gy. CONCLUSIONS: Radiation therapy is safe and effective for treatment of stage IVA uterine cervical cancer. The reduced radiation dose per fraction may contribute to the prevention of vesicovaginal fistula formation.

Radiation Therapy for Para-Aortic Lymph Node Metastasis from Uterine Cervical Cancer.

AIM: To evaluate the efficacy of radiation therapy for para-aortic lymph node metastases from uterine cervical cancer and to identify an optimal radiation regimen. PATIENTS AND METHODS: A total of 80 metastatic para-aortic lymph nodes, ranging from 11-50 mm (median=20 mm) on computed tomography, in 22 patients with squamous cell carcinoma of the uterine cervix were initially treated with radiation therapy. Total radiation doses for para-aortic lymph node metastases were 40-61.2 Gy (median=50.4 Gy) in 1.8-2 Gy fractions. RESULTS: Eight out of the 22 patients remained alive at a median follow-up of 32 months. Seven irradiated lymph nodes, 20-50 mm in diameter, in four patients progressed after irradiation at total doses of 44-50.4 Gy. No metastatic lymph nodes administered >50.4 Gy (median=55.8 Gy) exhibited progression after irradiation. All metastatic lymph nodes ≤ 25 mm in diameter irradiated with 50 or 50.4 Gy were controlled. The 3-year lymph node progression-free rates were 78% in the cohort of 22 patients and 89% considering all 80 metastatic lymph nodes. Apart from transient hematological reactions, two patients developed grade 3 or more therapy-related toxicities, including radiation proctitis in one and hemorrhagic cystitis and colitis in another. CONCLUSION: Radiation therapy can effectively control para-aortic lymph node metastases in patients with uterine cervical cancer. A total dose of 50.4 Gy in 1.8 Gy fractions is sufficient to control metastatic lymph nodes ≤ 25 mm in diameter, whereas a higher dose (approximately 55.8 Gy) may be required for larger nodes.

Tangent field technique of TomoDirect improves dose distribution for whole-breast irradiation.

TomoDirect (TD) is an intensity-modulated radiotherapy system that uses a fixed gantry angle instead of rotational beam delivery. Here, we investigated the effect of the multiple beam technique of TomoDirect on dose distribution compared with commonly-used tangential beams. We included 45 consecutive patients with right breast cancer who underwent postoperative radiotherapy in our institute in the present study. Clinical target volume (CTV) was the whole right breast. The planning target volume (PTV) was created by expanding the CTV by a 0.5 cm margin. Paired TD plans were generated for each patient; a two-beam plan using paired tangential beams and a six-beam plan with four additional beams with modified gantry angles of ± 5° from the original tangential beam set. A prescribed dose of 50 Gy was defined for 50% isodoses of the PTV. The six-beam plan delivered significantly more homogeneous doses to the PTV than the two-beam plan; and the mean dose to the PTV in the six-beam plan more closely reflected the prescribed dose. V20Gy and mean dose to the right lung and mean dose to the whole body were also significantly decreased in the six-beam plan. However, duration of radiation exposure was 1 min longer in the six-beam plan than in the two-beam plan. The dose distribution to the target and organs at risk were improved with the six-beam plan relative to the two-beam plan without increasing the whole-body radiation dose. The six-beam plan using TD is a simple technique that can be routinely applied to whole-breast irradiation in clinical practice.

Chronic catatonia with obsessive compulsive disorder symptoms treated with lorazepam, memantine, aripiprazole, fluvoxamine and neurosurgery.

Catatonia is a syndrome with protean manifestations and multiple aetiologies. In this report, the authors describe the case of a young woman who presented for care after a 13-year period of catatonia-like symptoms, including mutism, refusal to eat and persistent neck flexion. Medical management included placement of a percutaneous endoscopic gastric tube for nutritional support. A thorough medical investigation later revealed the presence of a cervical spine haemangioma that was treated surgically, with improvement in neck posturing. Psychopharmacological treatment included lorazepam, aripiprazole and memantine. Addition of fluvoxamine to target obsessive compulsive disorder (OCD)-like symptoms resulted in clinical improvement, suggesting OCD as a possible cause of this patient's chronic catatonic state.

Regulation of histone acetylation and transcription by nuclear protein pp32, a subunit of the INHAT complex.

Histone acetylation by p300/CBP and PCAF coactivators is considered to be a key mechanism of chromatin modification and transcriptional regulation. A multiprotein cellular complex, INHAT (inhibitor of acetyltransferases), containing the Set/TAF-Ibeta oncoprotein and pp32 strongly inhibits the HAT activity of p300/CBP and PCAF by histone masking. Here we report that the INHAT complex and its subunits have overlapping but distinct HAT inhibitory and histone binding characteristics. We provide evidence suggesting that the histone binding and INHAT activity of pp32 can be regulated by its physical association with other INHAT subunits. In vivo colocalization and transfection studies show that pp32 INHAT domains are responsible for histone binding, HAT inhibitory activity, and repression of transcription. We propose that INHAT and its subunits may function by modulating histone acetyltransferases through a histone-masking mechanism and may play important regulatory roles in the establishment and maintenance of the newly proposed "histone code" of chromatin.