Efficacy of Low-Dose Estrogen-Progestins and Progestins in Japanese Women with Dysmenorrhea: A Systematic Review and Network Meta-analysis.

INTRODUCTION: Although several studies suggest beneficial effects of low-dose estrogen-progestins (LEPs) and progestins on dysmenorrhea in Japanese women, the difference in efficacy between drugs remains unknown. METHODS: We identified studies by searching the MEDLINE, Cochrane Library, and ICHUSHI databases and included randomized controlled trials (RCTs) that used total dysmenorrhea score and visual analogue scale (VAS) as outcome measures to evaluate LEPs and progestins for primary and secondary dysmenorrhea. We analyzed results by meta-analysis and network meta-analysis (NMA). RESULTS: We identified 10 articles on eight RCTs and included seven drugs (six LEPs and one progestin, i.e., dienogest) and placebo in the analysis. Meta-analysis showed improvements in total dysmenorrhea score and VAS for almost all drugs compared with placebo. In NMA, VAS in secondary dysmenorrhea improved more with dienogest than with norethisterone/ethinylestradiol (mean difference - 25.84 [95% CrI - 44.46 to - 7.15]). In the comparison of administration regimens, VAS improved more with progestin-continuous than LEP-cyclic and the surface under the cumulative ranking (SUCRA) of LEP-extended and progestin-continuous appeared to be higher than that of LEP-cyclic. CONCLUSIONS: We confirmed that LEPs and dienogest are effective for primary and secondary dysmenorrhea and suggest that continuous regimens may be more effective than cyclic regimens in improving outcomes.

Safety and efficacy of panitumumab in combination with trifluridine/tipiracil for pre-treated patients with unresectable, metastatic colorectal cancer with wild-type RAS: The phase 1/2 APOLLON study.

BACKGROUND: We aimed to assess the safety and efficacy of combination treatment with panitumumab plus trifluridine/tipiracil (FTD/TPI) in patients with wild-type RAS metastatic colorectal cancer (mCRC) who were refractory/intolerant to standard therapies other than anti-epidermal growth factor receptor therapy. METHODS: APOLLON was an open-label, multicentre, phase 1/2 trial. In the phase 1 part, 3 + 3 de-escalation design was used to investigate the recommended phase 2 dose (RP2D); all patients in the phase 2 part received the RP2D. The primary endpoint was investigator-assessed progression-free survival (PFS) rate at 6 months. Secondary endpoints included PFS, overall survival (OS), overall response rate (ORR), disease control rate (DCR), time to treatment failure (TTF), and safety. RESULTS: Fifty-six patients were enrolled (phase 1, n = 7; phase 2, n = 49) at 25 Japanese centres. No dose-limiting toxicities were observed in patients receiving panitumumab (6 mg/kg every 2 weeks) plus FTD/TPI (35 mg/m2 twice daily; days 1-5 and 8-12 in a 28-day cycle), which became RP2D. PFS rate at 6 months was 33.3% (90% confidence interval [CI] 22.8-45.3). Median PFS, OS, ORR, DCR, and TTF were 5.8 months (95% CI 4.5-6.5), 14.1 months (95% CI 12.2-19.3), 37.0% (95% CI 24.3-51.3), 81.5% (95% CI 68.6-90.8), and 5.8 months (95% CI 4.29-6.21), respectively. Neutrophil count decreased (47.3%) was the most common Grade 3/4 treatment-emergent adverse event. No treatment-related deaths occurred. CONCLUSION: Panitumumab plus FTD/TPI exhibited favourable anti-tumour activity with a manageable safety profile and may be a therapeutic option for pre-treated mCRC patients.

Radiotherapy doses at special reference points correlate with the outcome of cervical cancer therapy.

PURPOSE: The authors analyzed the correlation between radiotherapy doses at reference points on the uterine edge and the rectal wall and both pelvic control and late rectal complications of cervical cancer therapy. METHODS AND MATERIALS: Between 1997 and 2005, 57 patients with Stages IB-IVA cancer of uterine cervix were treated with a combination of external beam radiotherapy and high-dose-rate intracavitary brachytherapy. Their high-dose-rate intracavitary brachytherapy was planned by dose-point optimization at six dose points located on the edge of uterus by computed tomography. A rectal reference point located on the anterior wall of the rectum by computed tomography was also used. The pelvic control rate and the rate of late rectal complications were calculated according to the biologically effective dose (BED) at each point and several clinical parameters. RESULTS: The overall 3-year pelvic control rate was 69.4%. The patients with a BED >80 Gy10 at the point on the edge of the uterine cervix had better pelvic control (78.4% at 3 years) than the patients with a BED < or =80 Gy10 (54.4% at 3 years), and the difference was significant. The difference in the BED (Gy3) at the rectal reference point between the patients with Grade 0-1 late rectal complications (median, 114 Gy) and the patients who developed Grade > or =2 late rectal complications (median, 178 Gy) was significant. Chemotherapy was a borderline significant parameter in regard to correlation with pelvic control and late rectal complications, but there were no correlations with other dosimetric or clinical parameters. CONCLUSIONS: The radiotherapy dose at the reference point on the edge of the cervix affected pelvic control more than the clinical parameters, and the dose at the rectal reference point was more strongly correlated with the occurrence of late rectal complications.

Correlation between single nucleotide polymorphisms and jejunal crypt cell apoptosis after whole body irradiation.

PURPOSE: To identify loci concerned with radiosensitivity in a mouse model using single nucleotide polymorphism (SNP) markers. MATERIALS AND METHODS: We subjected 276 second filial generation (F2) mice descended from two inbred mouse strains, radiation-induced apoptosis sensitive C57BL/6JNrs (B6) and radiation-induced apoptosis resistant C3H/HeNrs (C3H), to 2.5 Gy whole-body irradiation. We quantified jejunal crypt apoptosis, performed a genome-wide survey, and identified quantitative trait loci (QTL) associated with radiation sensitivity. We expressed apoptosis levels as an apoptotic score (AS), which was equal to the number of apoptotic bodies divided by the number of crypts. We genotyped the mice for 109 SNP markers. RESULTS: AS values were 97.7+/-32.9 in B6 mice and 49.0+/-24.9 in C3H mice (p < 0.01). Genome-wide analysis revealed 8 markers (2 on chromosome 9, 4 on 15, 1 on 17, and 1 on 18) affecting radiation-induced jejunal apoptosis with log odds (LOD) scores ranging from 2.11+/-3.91. We found a significant locus on chromosome 15, which was previously reported by Weil and colleagues. CONCLUSION: These findings support the view that the radiosensitivity of clinically normal tissue depends on variations in several genes.

Acute and late genitourinary toxicity of conformal radiotherapy for prostate cancer.

PURPOSE: The aim of this study was to identify predictive factors for genitourinary (GU) toxicity in prostate cancer patients who underwent conformal radiotherapy (CRT). MATERIALS AND METHODS: In this study we analyzed 154 cases of T1-3N0M0 prostate adenocarcinoma and evaluated the occurrence rate of acute and late GU toxicity and the duration of acute toxicity according to clinical parameters: age, transurethral resection of the prostate prior to CRT, hormone therapy, CRT dose, length of planning target volume (PTV). RESULTS: Altogether, 41% of the patients developed grade 2 or higher acute GU toxicity. Longer PTV was significantly associated with a higher incidence of acute GU toxicity (>7 cm, 53%;

Inter-strain variance in late phase of erythematous reaction or leg contracture after local irradiation among three strains of mice.

AIM: To gain insights into inter-strain differences in radiosensitivity. METHODS: Mice of inbred strains, A/J, C57BL/6J, and C3H/HeMs, were irradiated at graded doses ranging from 20 to 60 Gy. Skin reaction and leg contraction were observed for a period of 230 days and between 175 and 350 days, respectively. Gene expressions in leg skin tissue were quantified by quantitative RT-PCR assay at 1, 12 and 72 h after 30 Gy irradiation. Mice were locally irradiated by using a Cs-137 source. RESULTS: The three strains showed various degrees of susceptibility to irradiation has evaluated by skin scores. Large inter-strain differences were also detected in the lengths of contraction. Expressions of several genes such as Per3 and Rad51ap1 displayed inter-strain differences. CONCLUSIONS: The continuum model of tissue injury revealed that genetic factor, which varies among strains, is one of the causes of variances in severity of damage after irradiation.

Large duodenal somatostatinoma in the third portion associated with severe glucose intolerance.

A 51-year-old man was admitted with hyperglycemia and a duodenal tumor. Although his glycemic control was poor, basal C-peptide levels were not suppressed. Further examination revealed a mass measuring 7.8 cm in diameter in the third portion of the duodenum. Duodenectomy revealed a slow-growing sessile tumor located near Treitz's ligament. The immunohistochemical profile of sections of the specimen revealed the presence of somatostatin. The patient's serum somatostatin was elevated to 300 pg/ml preoperatively, but was reduced to 10 pg/ml postoperatively. Glycemic control also normalized after the operation.

Pasteurella multocida septicemia caused by close contact with a domestic cat: case report and literature review.

We report here a case of Pasteurella multocida infection caused by cat exposure presenting with septic shock, sinusitis, and pneumonia. The patient was a febrile 20-year-old woman who had been experiencing disturbed consciousness progressively. She had close contact with a domestic cat and had received some scratches on both arms. A magnetic resonance imaging (MRI) scan of the head showed a high intensity in the paranasal cavity, and a computed tomographic (CT) scan of the chest showed bilateral lung consolidations. The pathogen was identified as P. multocida by the cultures from blood and nasal discharge. She was given intensive antibiotic therapy with ceftriaxone and piperacillin, continuous hemodiafiltration (CHDF) therapy, and anticoagulation therapy. Owing to these therapeutic regimens, the septic shock was successfully treated without complications. We also review the literature on P. multocida septicemia.