The impact of baseline [−2]proPSA-related indices on the prediction of pathological reclassification at 1 year during active surveillance for low-risk prostate cancer: the Japanese multicenter study cohort

Purpose

Active surveillance (AS) is one potential solution to avoiding the overtreatment of favorable prostate cancer. By handling the AS strategy more safely, tumor aggressiveness may be evaluated more accurately. The aim of the present study was to evaluate the predictive impact of baseline prostate-specific antigen (PSA) isoform [?2]proPSA (p2PSA)-related indices on the pathological reclassification at 1 year during an AS program.

Methods

Between 2002 and 2003, 134 males diagnosed with low-risk prostate cancer were registered in the Japanese multicenter study cohort as candidates for AS, and 118 (88 %) males actually proceeded to AS. Of the 118 patients, the 67 that underwent protocol biopsy at 1 year after beginning AS were enrolled in the present study. The predictive significance of various baseline clinicopathological features and p2PSA-related indices on pathological reclassification at 1 year after beginning AS were investigated.

Results

The pathological reclassification rate was 37.3 %. According to the univariate analysis, prostate volume (p = 0.049), number of biopsy cores (p = 0.047), percentage of positive biopsy cores (p = 0.023), p2PSA to free PSA ratio (%p2PSA) (p = 0.003) and prostate health index (phi) (p = 0.010) at baseline were significantly different between the reclassification and non-reclassification groups. By multivariate logistic regression analysis, baseline %p2PSA (p = 0.008) and phi (p = 0.008) were the only independent predictive factors for pathological upgrade at 1 year after AS commencement.

Conclusions

Baseline %p2PSA and phi may predict the pathological reclassification at 1 year after starting AS, which could be due to the under detection of clinically significant prostate cancer at AS enrollment.     

Influence of genetic polymorphisms and habitual caffeine intake on the changes in blood pressure,pulse rate,and calculation speed after caffeine intake: A prospective,double blind,randomized trial in healthy volunteers

The aim of this study was to investigate the contribution of gene polymorphisms, in combination with habitual caffeine consumption, to the effect of caffeine intake on hemodynamic and psychoactive parameters. A double-blind, prospective study was conducted with 201 healthy volunteers randomly allocated 2:1 to the caffeinated group (150 mL decaffeinated coffee with additional 200 mg caffeine) or decaffeinated group (150 mL decaffeinated coffee). We measured the changes in blood pressure (BP) and calculation speed upon coffee intake, stratifying with gene polymorphisms, e.g., those in adenosine A_2A receptor (ADORA2A) and cytochrome P450 (CYP) 1A2, and daily caffeine consumption (≤90 mg/day and >90 mg/day). Overall, caffeine intake independently increased BP and calculation speed (p-values < 0.05), irrespective of the polymorphisms. In stratified analysis, a statistical significance within the caffeinated group was observed for the change in systolic BP in the stratum of CYP1A2 polymorphism with daily caffeine consumption ≤90 mg/day: change in systolic BP in the CYP1A2 rs762551 CC group (mean ± SD = 11.8 ± 5.9) was higher than that in the AA/CA group (4.1 ± 5.5). Gene polymorphisms may limitedly modify the effect of caffeine intake on hemodynamic parameters in combination with habitual caffeine consumption.     

Clonal leukemic evolution in myelodysplastic syndromes with TET2 and IDH1/2 mutations

Somatic mutations of TET2, IDH1, and IDH2 have been described in myelodysplastic syndrome. The impact of these mutations on outcome of myelodysplastic syndrome and their progression to secondary acute myeloid leukemia remains unclear. Mutation status of TET2, IDH1 and IDH2 was investigated in a cohort of 46 paired myelodysplastic syndrome/acute myeloid leukemia samples and 122 non-paired cases with de novo myelodysplastic syndrome, to clarify their roles in the evolution of myelodysplastic syndrome to acute myeloid leukemia. Among the 168 de novo myelodysplastic syndrome patients, the frequency of TET2, IDH1, and IDH2 mutations was 18.5%, 4.2% and 6.0%, respectively. TET2/IDH mutations had no impact on survivals, while TET2 mutations were significantly associated with rapid progression to acute myeloid leukemia. Seventeen of the 46 paired myelodysplastic syndrome/secondary acute myeloid leukemia samples harbored TET2/IDH mutations; none acquired these mutations in acute myeloid leukemia phase. Progression to acute myeloid leukemia was accompanied by evolution of a novel clone or expansion of a minor pre-existing subclone of one or more distinct mutations in 12 of the 17 cases with TET2/IDH mutations. A minor subclone in 3 cases with biallelic TET2 inactivation subsequently expanded, indicating biallelic TET2 mutations play a role in acute myeloid leukemia progression. Twelve patients acquired other genetic lesions, and/or showed increased relative mutant allelic burden of FLT3-ITD, N/K-RAS, CEBPA or RUNX1 during acute myeloid leukemia progression. Our findings provide a novel insight into the role of TET2/IDH mutation in the pathogenesis of myelodysplastic syndrome and subsequent progression to acute myeloid leukemia.     

CO2 pneumoperitoneum increases secretory IgA levels in the gut compared with laparotomy in an experimental animal model

Background

Secretory immunoglobulin A (s-IgA) plays an important role in both gut and systemic immunity. This study aimed to investigate the production of s-IgA resulting from a CO₂ pneumoperitoneum compared with a laparotomy.

Methods

Using enzyme-linked immunosorbent assays, s-IgA in stool, malondialdehyde (MDA), and Toll-like receptor 4 (TLR4) in the ileal tissue were evaluated as markers for gut and systemic immune responses in an animal model. The rats were randomly divided into (i) anesthesia-only as the control group; (ii) laparotomy-only as the open group; and (iii) CO₂ pneumoperitoneum-only as the pneumoperitoneum group. To evaluate the gut immune system in a time-dependent manner, each group was further divided into short- and long-time subgroups.

Results

s-IgA levels did not increase in the open group but significantly increased in the pneumoperitoneum group compared with the control group (p < 0.05). In addition, s-IgA levels in the long-time subgroup significantly increased compared with the short-time subgroup of the pneumoperitoneum group (p < 0.05). TLR4 levels steeply and gradually increased in the open and pneumoperitoneum groups, respectively. MDA levels in the pneumoperitoneum group increased during the early phase and were significantly higher than those in the open group at 24 h (p < 0.05).

Conclusions

This study demonstrated that s-IgA levels in stool increased in the pneumoperitoneum group compared with the open group, suggesting that CO₂ pneumoperitoneum may cause transitory damage to the intestinal mucosa.     

Alpha‐actinin‐4 (ACTN4) gene amplification is a predictive biomarker for adjuvant chemotherapy with tegafur/uracil in stage I lung adenocarcinomas

Although adjuvant tegafur/uracil (UFT) is recommended for patients with completely resected stage I non‐small‐cell lung cancer (NSCLC) in Japan, only one‐third of cases has received adjuvant chemotherapy (ADJ) according to real‐world data. Therefore, robust predictive biomarkers for selecting ADJ or observation (OBS) without ADJ are needed. Patients who underwent complete resection of stage I lung adenocarcinoma with or without adjuvant UFT were enrolled. The status of ACTN4 gene amplification was analyzed by FISH. Statistical analyses to determine whether the status of ACTN4 gene amplification affected recurrence‐free survival (RFS) were carried out. Formalin‐fixed, paraffin‐embedded samples from 1136 lung adenocarcinomas were submitted for analysis of ACTN4 gene amplification. Ninety‐nine (8.9%) of 1114 cases were positive for ACTN4 gene amplification. In the subgroup analysis of patients aged 65 years or older, the ADJ group had better RFS than the OBS group in the ACTN4‐positive cohort (hazard ratio [HR], 0.084, 95% confidence interval [CI], 0.009‐0.806; P = .032). The difference in RFS between the ADJ group and the OBS group was not significant in ACTN4‐negative cases (all ages: HR, 1.214; 95% CI, 0.848‐1.738; P = .289). Analyses of ACTN4 gene amplification contributed to the decision regarding postoperative ADJ for stage I lung adenocarcinomas, preventing recurrence, improving the quality of medical care, preventing the unnecessary side‐effects of ADJ, and saving medical costs.     

Novel vaginoplasty technique involving the use of peritoneal flaps during laparoscopic radical hysterectomy for early-stage cervical cancer

Radical hysterectomy is often performed to treat early-stage cervical cancer in women of reproductive age, and sexual dysfunction due to postoperative vaginal shortening is a major concern [^1,2]. Vaginoplasty using various techniques is commonly performed in patients with congenital vaginal agenesis [³]. However, there are few reports of vaginoplasty being performed for vaginal shortening after radical hysterectomy in a patient with cervical cancer [^4,5]. We demonstrate a novel vaginoplasty technique in which peritoneal flaps are used during laparoscopic radical hysterectomy to prevent postoperative vaginal shortening and consequent sexual dysfunction in patients with early-stage cervical cancer. A 37-year-old woman with early-stage cervical cancer who wished to perform sexual activity postoperatively underwent laparoscopic radical hysterectomy and vaginoplasty. After radical hysterectomy, the residual vaginal length was 4 cm. The dissected peritoneum of pouch of Douglas (posterior peritoneal flap) was sutured to the posterior vaginal stump. The supravesical peritoneum was dissected from the ventral to the dorsal side to create an anterior peritoneal flap, which was inverted, pulled down, and sutured to the anterior vaginal stump. The anterior peritoneal flap and suprarectal peritoneum were sutured to create a 10-cm neovaginal vault. Subsequently, a methacrylic resin mold was inserted into the neovagina to prevent postoperative neovaginal stenosis. The patient had sexual intercourse 3 months postoperatively. She was satisfied with the sexual activity and experienced no vaginal shortening or stenosis. Our novel vaginoplasty technique is feasible and effective for preventing sexual dysfunction by lengthening the vagina during laparoscopic radical hysterectomy for early-stage cervical cancer.Trial RegistrationJapan Registry of Clinical Trials Identifier: jRCT1030210227     

Evolutionary‐adaptive and nonadaptive causes of infant attack/desertion in mammals: Toward a systematic classification of child maltreatment

Behaviors comparable to human child maltreatment are observed widely among mammals, in which parental care is mandatory for offspring survival. This article first reviews the recent findings on the neurobiological mechanisms for nurturing (infant caregiving) behaviors in mammals. Then the major causes of attack/desertion toward infants (conspecific young) in nonhuman mammals are classified into five categories. Three of the categories are ‘adaptive’ in terms of reproductive fitness: (i) attack/desertion toward non‐offspring; (ii) attack/desertion toward biological offspring with low reproductive value; and (iii) attack/desertion toward biological offspring under unfavorable environments. The other two are nonadaptive failures of nurturing motivation, induced by: (iv) caregivers’ inexperience; or (v) dysfunction in caregivers’ brain mechanisms required for nurturing behavior. The proposed framework covering both adaptive and nonadaptive factors comprehensively classifies the varieties of mammalian infant maltreatment cases and will support the future development of tailored preventive measures for each human case. Also included are remarks that are relevant to interpretation of available animal data to humans: (1) any kind of child abuse/neglect is not justified in modern human societies, even if it is widely observed and regarded as adaptive in nonhuman animals from the viewpoint of evolutionary biology; (2) group‐level characteristics cannot be generalized to individuals; and (3) risk factors are neither deterministic nor irreversible.     

Helical computed tomographic angiography in obstructed total anomalous pulmonary venous drainage

Helical computed tomographic angiography with differential color imaging technique clearly demonstrated pulmonary venous obstruction in an infant with total anomalous pulmonary venous drainage before and after operation. This technique is less invasive and provides precise spatial information of complicated vascular anomalies.     

Laparoscopy-assisted Billroth-I gastrectomy (LADG) for cancer: our 10 years' experience

To evaluate laparoscopy-assisted Billroth-I gastrectomy (LADG), we examined the outcome of its use over the last 10 years. From December 1991 to December 2001, 116 patients with early gastric cancer underwent LADG in the surgical department of Oita Medical University and Koga hospital by the same surgical staffs. An operation record and clinical sheets were reviewed to obtain the operative findings, clinical course, and pathologic findings of resected specimens to evaluate the usefulness of LADG in the management of early gastric cancer. In all LADG procedures, regional lymph nodes dissection (D1+alpha) was successfully performed using laparoscopy. The mean operative duration and blood loss were 234 minutes and 139 mL, respectively. There were only four major complications, including pneumonia, leakage of anastomosis, pancreatic injury, and anastomotic stenosis, but all these cases were successfully treated conservatively. The mean length of postoperative stay was 16.3 +/- 2.5 days. All patients except one, who died not of cancer but of cerebral bleeding, were alive without recurrence or port-site metastasis during mean follow-up period of 45 months. We successfully performed 116 LADG procedures over 10 years. This procedure is recommended for the treatment of patients with early gastric cancer because of the associated good prognosis and several benefits, including less invasiveness and early recovery.