Distribution of cervical intraepithelial neoplasia is closely associated with HPV status and uterine position.

Although cervical intraepithelial neoplasia (CIN) lesions are considered to be not randomly distributed across the cervix, but predominantly in the anterior wall, the clinicopathological etiology remains unknown. Herein, we aimed to elucidate the relationship between quantitatively measured area of CIN2/3 and cervical cancer associated factors by retrospective cohort study. We analyzed 235 consecutive therapeutic conization specimens dissected as a single intact section to determine CIN2/3 area and its correlation with both clinical risk factors including human papillomavirus (HPV) status (single or multiple infection) and uterine position defined by transvaginal ultrasound. Cervical wall was classified into three groups: anterior: (11, 12, 1, and 2 o'clock), posterior (5, 6, 7, and 8 o'clock) and lateral (3, 4, 9, and 10 o'clock). Multiple regression revealed that younger age and HPV16 status were significantly correlated with CIN2/3 area (p = 0.0224 and p = 0.0075, respectively). The Jonckheere-Terpstra test showed a significant trend: CIN2/3 area was highest in the single HPV16 group, followed by the multiple HPV16 group and the non-HPV16 group (p < 0.0001). CIN2/3 area in the anterior wall was statistically significantly larger than the posterior and lateral wall (p = 0.0059 and p = 0.0107, respectively). CIN2/3 area in the anterior wall was significantly greater with anteversion-anteflexion than retroversion-retroflexion (p = 0.0485), whereas CIN2/3 area in the posterior wall was significantly larger with retroversion-retroflexion than anteversion-anteflexion (p = 0.0394). In conclusion, the topographical distribution of CIN2/3 area is closely associated with patient age, high-risk HPV status, especially single HPV16 infection and uterine position.

Comparison of complete resection rates in cold snare polypectomy using two different wire diameter snares: A randomized controlled study.

BACKGROUND AND AIM: Cold snare polypectomy (CSP) is a standard treatment for small colorectal polyps. This study examined the effect of different snare wire diameters on complete histological resection rate, resection depth, and CSP safety. METHODS: This randomized controlled trial was conducted at two institutions between June 2019 and March 2021. Eligible colorectal polyps (≤10 mm) were randomly assigned in a 1:1 ratio to receive either CSP with a conventional snare made of normal-diameter wire (0.40 mm) or CSP with a dedicated snare made of thin wire (0.23 mm). The primary endpoint was the complete resection rate determined on histological assessment of the resected specimen. RESULTS: In total, 254 lesions in 152 patients were included, with 128 and 126 lesions assigned to the normal-diameter wire snare group and the thin-wire snare group, respectively. No significant differences were observed in patient characteristics between the two groups. The histological complete resection rate was significantly higher in the thin-wire snare group than in the normal-diameter wire snare group (70.0% vs 81.0%, P = 0.04). The normal-diameter wire snare group had significantly more cases of unclear horizontal margin evaluation than the thin-wire snare group (28.1% vs 15.9%, P = 0.02). No significant differences were observed between the two groups in the muscularis mucosa and submucosa of the resected specimens or the thickness of the submucosa in the resected specimens. CONCLUSIONS: CSP with a dedicated thin-wire snare provides more specimens that can be evaluated at the horizontal end and increases the histological complete resection rate.

Perinatal Management in a Pregnant Woman with Ureteropelvic Junction Obstruction: Case Report and Literature Review.

Although giant hydronephrosis (GH) associated with ureteropelvic junction obstruction (UPJO) is extremely rarely detected in pregnant women, diagnostic methods, therapeutic approaches, and perinatal management have not been established. A 31-year-old Japanese primipara had a 15 cm × 12 cm multi-cystic mass in the right abdomen detected by transabdominal ultrasound at gestational week 26. Magnetic resonance imaging revealed that the mass was right renal GH. She underwent serial ultrasound-guided transretroperitoneal drainage as conservative treatment. She delivered vaginally at gestational week 36. Since she had flank pain and a documented non-functional right kidney, laparoscopic nephrectomy was conducted 22 months after delivery. UPJO with fewer smooth muscle cells and fibrosis was histologically diagnosed in the surgical specimen. Her postpartum and postoperative courses were uneventful for 10 months. We performed a literature review of diagnostic methods, clinical characteristics, and perinatal management in pregnant women with GH due to UPJO.

Stereospecific reduction of the butenolide in strigolactones in plants.

Reductive metabolism of strigolactones (SLs) in several plants was investigated. Analysis of aquaculture filtrates of cowpea and sorghum each fed with four stereoisomers of GR24, the most widely used synthetic SL, revealed stereospecific reduction of the double bond at C-3' and C-4' in the butenolide D-ring with preference for an unnatural 2'S configuration. The cowpea metabolite converted from 2'-epi-GR24 and the sorghum metabolite converted from ent-GR24 had the methyl group at C-4' in the trans configuration with the substituent at C-2', different from the cis configuration of the synthetic H2-GR24 reduced with Pd/C catalyst. The plants also reduced the double bond in the D-ring of 5-deoxystrigol isomers with a similar preference. The metabolites and synthetic H2-GR24 stereoisomers were much less active than were the GR24 stereoisomers in inducing seed germination of the root parasitic weeds Striga hermonthica, Orobanche crenata, and O. minor. These results provide additional evidence of the importance of the D-ring for bioactivity of SLs.

Width and depth of resection for small colorectal polyps: hot versus cold snare polypectomy.

BACKGROUND AND AIMS: Curability is associated with resection width and depth in polypectomy. We evaluated the resection width and depth achieved with hot snare polypectomy (HSP) and cold snare polypectomy (CSP) for small colorectal polyps. METHODS: In this single-center, prospective, randomized controlled study, patients with rectal or rectosigmoid polyps ≤10 mm in diameter were treated with HSP or CSP. Resection width was evaluated as mucosal defect size, measured immediately postprocedure and 1 day later. Resection depth was histologically evaluated using obtained specimens. RESULTS: Fifty-two patients were enrolled. Mean lesion size was 5.6 mm with HSP (n = 27) and 5.8 mm with CSP (n = 25). Mean mucosal defect diameter immediately after HSP and CSP was 5.1 mm and 7.5 mm, respectively (P < .001). The diameter 1 day after the procedure increased by 29% (95% confidence interval [CI], 17%-41%) with HSP and decreased by 25% (95% CI, 18%-32%) with CSP (P < .001). Muscularis mucosa was obtained similarly with HSP and CSP (96% [95% CI, 82%-99%] vs 92% [95% CI, 75%-98%]; P = .603). Submucosal tissue was obtained significantly more frequently with HSP than with CSP (81% [95% CI, 63%-92%] vs 24% [95% CI, 11%-43%]; P < .001). CONCLUSIONS: The resection width immediately after CSP was larger than that after HSP but was significantly smaller at day 1 after resection. Although the resection depth after CSP was more superficial, muscularis mucosa was obtained in most specimens. Thus, CSP has sufficient resection width and depth to enable complete polyp resection and potentially has a superior safety profile than HSP.

[A Case of Giant Prostate Carcinoma Effectively Treated with External-Beam Radiation Therapy].

We present a case of gigantic prostate tumor in a patient with castration-resistant prostate cancer with successful local control by external-beam radiation therapy. A 71-year-old man was shown to have a prostate specific antigen (PSA)level of 24.5 ng/ml, Gleason 9, cT2N1M1a, prostate adenocarcinoma with an estimated prostate volume of 26.9 g. He achieved a PSA nadir at 4 months after the initial androgen deprivation therapy and was diagnosed with castration-resistant prostate cancer three years later. Eight months after the diagnosis of castration-resistant prostate cancer, he visited our hospital due to urinary retention. Abdominal computed tomography scan showed a gigantic prostatic mass occupying the whole pelvic cavity along with multiple lymph node, bone and liver metastases. The estimated volume of the prostate was 878 g. A tumor needle biopsy revealed a histological finding similar to the initial prostate biopsy which was adenocarcinoma with Gleason 9. He underwent external beam radiation therapy (60 Gy) to the prostate, which brought about excellent local control with a 96.7% shrinkage of tumor at 2 months after radiation therapy. He had no complaints of urinary symptoms and no need for urethral catheterization until he died of prostate cancer metastases.

Weaving hypothesis of cardiomyocyte sarcomeres: discovery of periodic broadening and narrowing of intercalated disk during volume-load change.

To investigate how cardiomyocytes change their length, echocardiographic and morphological studies were performed on rabbit hearts that were subjected to volume overload, overload removal, and repeated cycles of overload and overload removal. These conditions were created by arterio-venous fistula between the carotid artery and jugular vein, closure of the fistula, and cycles of repeatedly forming and closing fistula, respectively. After overload, hearts dilated and myocytes elongated. Intercalated disks repeatedly broadened and narrowed with a 2-day cycle, which continued for 8 weeks in many animals. The cycle consisted of shifts between five modes characterized by two interdigitation elongation-and-shortenings as follows: (I) flat with short ( approximately 1/4 to approximately 1/3 sarcomere long) interdigitations; (II) flat with long (one sarcomere long) interdigitations; (III) grooved with short interdigitations; (IV) grooved with long interdigitations; (V) flat with short interdigitations intermingled by sporadic long interdigitations; and return to (I). After overload removal, hearts contracted and myocytes shortened with similar 2-day broadening and narrowing cycle of intercalated disks, in which the five modes were reversed. Repeated overload and overload removal resulted in the repetition of myocyte elongation and shortening. We hypothesize that a single elongation-and-shortening event creates or disposes one sarcomere layer, and the two consecutive elongation-and-shortenings occur complementarily to each other so that the disks return to their original state after each cycle. Our hypothesis predicts that intercalated disks weave and unravel one sarcomere per myocyte per day.

Side-to-side linking of myocardial cells in hypertrophic cardiomyopathy: whole heart microscopic observation with tangential sections.

By cross-section or longitudinal section, it is difficult to investigate longitudinal features of myocardial cells in the whole heart. Here, introducing the use of tangential sections to obtain longitudinal aspect of myocardial cells in any part of myocardium, the authors evaluated myocardium in the left ventricle in 10 normal hearts and four hearts with hypertrophic cardiomyopathy (HCM). Tangential sections were obtained by peeling the superficial layer of myocardium. After peeling the whole surface, secondary deep layer was peeled. These procedures were repeated more than five times through the wall. Intercalated discs (ICD) were observed immunohistochemically with anti-N-cadherin and antidesmoplakin. In normal hearts, myocardial cells were cut longitudinally and ran parallel in tangential sections. They linked end-to-end with simple and regular ICD with average lengths of 120-130 microm and average sarcomere numbers of 56-65. In HCM hearts, many myocardial cells were cut almost longitudinally running approximately parallel in tangential sections. Myocardial cells frequently showed side-to-side linking characterized by skewed ICD, indistinct ICD counterparts, and longitudinally arranged ICD. Two young HCM hearts had circle-shaped ICD and vacuole-like structures highlighted by immunostaining for N-cadherin, which were actually extracellular structures comparable with irregular side-to-side linking. It is considered that side-to-side linking of myocardial cells is a characteristic microscopic feature in HCM rather than myocardial disarray.

Normalization of high-flow or removal of flow cannot stop high-flow induced endothelial proliferation.

Endothelial cells (ECs) are activated in response to high-flow. Our previous studies using arteriovenous fistula (AVF) model have demonstrated that high-flow in blood vessels induces an early and rapid proliferation of ECs before arterial dilatation. Here, we investigated the proliferation of ECs, which had once been stimulated by high-flow loading, in a situation without the influence of high-flow. First, we induced high-flow in the rabbit common carotid artery by using AVF. Then, we removed the influence of high-flow by normalization of high-flow with the closure of AVF or by removal of flow itself with tissue isolation and organ culture or with cell culture of ECs, at the timing considered that ECs began to proliferate. Kinetics of ECs was investigated by a laser scanning confocal microscopy, phase-contrast microscopy and light microscopy using bromodeoxyuridine labeling method. We found that ECs, which had once been stimulated by high-flow, transiently proliferated even after normalization of high-flow or removal of flow. We assume that proliferation of ECs is promised when these cells start to proliferate after high-flow loading.

Risk factors of sudden death in the Japanese hot bath in the senior population.

A series of experiments were carried out to clarify the cause of death and the risk factors related to sudden death in the Japanese senior population while bathing in a Japanese style "hot bath." The biodynamic changes while bathing were carefully monitored under actual bathing situations occurring in both the winter and summer seasons. We observed double product (DP), total peripheral blood vessel resistance (TPR), cardiac output (CO), and blood vessel compliance (COMP) by measuring blood pressure, heart rate, pulse wave, and electrocardiogram (ECG). The finding of a high level of DP in the elderly suggests that more myocardial oxygen consumption is needed than for young adults, particularly in subjects with arrhythmia. Although the values for TPR and CO changed somewhat during bathing, the changes were considered normal and to be expected. However, more significant and substantial changes were observed during the winter experiment than during the summer experiment, no doubt owing to lower temperature of the bathing room. The value of COMP did not vary significantly between winter and summer subjects. Twelve subjects in the elderly developed ECG changes while bathing such as supraventricular extrasystole or ventricular tachycardia. No clinical significance was found in the biochemical analyses of the blood obtained before and after bathing. In conclusion, some subjects in the elderly showed risky changes in the above parameters and ECG, factors which may partially explain some of the causes of the many reported cases of lapse of consciousness and unexpected sudden death in the elderly while bathing especially in the winter season. Cold climate, hot water immersion, and hydrostatic pressure may affect their physiological compensation along with existing of coronary stenosis or weakness of respiratory function as a normal consequence of advanced age.

Forensic consideration of death in the bathtub.

About 100-120 cases of 'sudden death in bathroom' are reported every year in our prefecture, which is 8-10% of the total number of what is considered unnatural deaths. For reasons that are still unclear, the victims die while bathing in the bathtub. This baffling form of death occurs mostly in the winter season and 80-% of these are elderly persons. However, despite a full autopsy, it is sometimes still very difficult to determine the cause of death or the direct cause of drowning in the bathtub. To prevent others from this mysterious form of death and to determine the risk factors for the elderly while bathing, we examined several parameters such as physiological changes and biochemical blood analysis in a total of 54 volunteers during both the winter and summer seasons in Japan. We found that some of the elderly developed cardiac arrhythmia such as ventricular tachycardia, ventricular extrasystole, supraventricular extrasystole, and bradycardia. Also, decreases of systolic blood pressure during bathing were observed during this experiment. We conclude that the development of extrasysytole or ventricular tachycardia can be a stress involved in bathing. These changes might contribute to cardiac arrest or to drowning in the bathtub. Moreover, a sudden decrease of blood pressure is considered to be a risk factor of cerebrovascular accident.