Technical tips for intersphincteric resection: how to take out the rectum

Intersphincteric resection (ISR) is an ideal technique that preserves the anus, regardless of whether the internal anal sphincter is removed. However, it is difficult to dissect the anterior wall of the rectum from the adjacent organs. We herein describe a safe and useful ISR technique which draws out the rectum through the anus. The intersphincteric space (ISS) between the internal and external anal sphincter muscles was first transabdominally dissected. Next, the transanal dissection was advanced into the ISS bilaterally from the posterior side without dissecting the anterior wall of the anal canal, and the sigmoid colon and rectum were drawn out through the anus. Dissection between the anterior wall of the rectum and prostate/vagina could be easily performed under direct vision. This technique enables the dissection without any risk of a positive surgical margin or unexpected bleeding, and avoids injury to adjacent organs. This technique seems to be a safe and useful dissection technique for approaching the anterior wall of the anal canal.     

Comprehensive analysis of intravascular ultrasound and angiographic morphology of culprit lesions between ST-segment elevation myocardial infarction and non-ST-segment elevation acute coronary syndrome

Background

Some plaques lead to ST-segment elevation myocardial infarction (STEMI), whereas others cause non-ST-segment elevation acute coronary syndrome (NSTEACS). We used angiography and intravascular ultrasound (IVUS) to investigate the difference of culprit lesion morphologies in ACS.

Methods

Consecutive 158 ACS patients whose culprit lesions were imaged by preintervention IVUS were enrolled (STEMI = 81; NSTEACS = 77). IVUS and angiographic findings of the culprit lesions, and clinical characteristics were compared between the groups.

Results

There were no significant differences in patients' characteristics except for lower rate of statin use in patients with STEMI (20% vs 44%, p = 0.001). Although angiographic complex culprit morphology (Ambrose classification) and thrombus were more common in STEMI than in NSTEACS (84% vs 62%, p = 0.002; 51% vs 5%, p < 0.0001, respectively), SYNTAX score was lower in STEMI (8.6 ± 5.4 vs 11.5 ± 7.1, p = 0.01). In patients with STEMI, culprit echogenicity was more hypoechoic (64% vs 40%, p = 0.01), and the incidence of plaque rupture, attenuation and “microcalcification” were significantly higher (56% vs 17%, p < 0.0001; 85% vs 69%, p = 0.01; 77% vs 61%, p = 0.04, respectively). Furthermore, the maximum area of ruptured cavity, echolucent zone and arc of microcalcification were significantly greater in STEMI compared with NSTEACS (1.80 ± 0.99 mm² vs 1.13 ± 0.86 mm², p = 0.006; 1.52 ± 0.74 mm² vs 1.21 ± 0.81 mm², p = 0.004; 99.9 ± 54.6° vs 77.4 ± 51.2°, p = 0.01, respectively). Quantitative IVUS analysis showed that vessel and plaque area were significantly larger at minimum lumen area site (16.6 ± 5.4 mm² vs 14.2 ± 5.5 mm², p = 0.003; 13.9 ± 5.1 mm² vs 11.6 ± 5.2 mm², p = 0.003, respectively).

Conclusion

Morphological feature (outward vessel remodeling, plaque buildup and IVUS vulnerability of culprit lesions) might relate to clinical presentation in patients with ACS.     

Intravascular ultrasound morphology of culprit lesions and clinical demographics in patients with acute coronary syndrome in relation to low-density lipoprotein cholesterol levels at onset

Despite current standards of care aimed at achieving targets for low-density lipoprotein cholesterol (LDL-C), many patients remain at high residual risk of cardiovascular events. We sought to assess the LDL-C-dependent differences in culprit intravascular ultrasound (IVUS) morphologies and clinical characteristics in patients with acute coronary syndrome (ACS). Eighty-six consecutive ACS patients whose culprit lesions imaged by preintervention IVUS were divided into two groups based on the fasting LDL-C level on admission: a low-LDL-C group (LDL-C <2.6 mmol/l, n = 45) and a high-LDL-C group (LDL-C ≥2.6 mmol/l, n = 41). Patients with stable angina with LDL-C <2.6 mmol/l (n = 30) were also enrolled as an age- and gender-matched control. The low-LDL-C ACS group was significantly older (72 ± 12 vs 64 ± 14 years, P = 0.007) and more diabetic (47 % vs 15 %, P = 0.001). Importantly, IVUS morphologies were comparable between low- and high-LDL-C ACS groups (all P not significant), whereas culprit plaque was more hypoechoic and less calcified in the low-LDL-C ACS group than in the low-LDL-C stable angina group. Furthermore, compared with the low-LDL-C ACS nondiabetic group, the low-LDL-C ACS diabetic group was more obese, more triglyceride rich (1.3 ± 0.6 vs 0.9 ± 0.4 mmol/l, P = 0.003), and more endothelially injured, but no different for the culprit IVUS morphologies. In multivariate analysis, diabetes was independently associated with a low LDL-C level on admission in patients with ACS. There was no relationship between the LDL-C level at onset and culprit-plaque IVUS morphologies in ACS patients, although culprit plaque in the low-LDL-C ACS group was more vulnerable than in the low-LDL-C stable angina group. In patients with low-LDL-C levels, diabetes with atherogenic dyslipidemia might be the key residual risk.     

RANKL-induced CCL22/macrophage-derived chemokine produced from osteoclasts potentially promotes the bone metastasis of lung cancer expressing its receptor CCR4

Chemokines are now known to play an important role in cancer growth and metastasis. Here we report that differentiating osteoclasts constitutively produce CCL22 (also called macrophage-derived chemokine) and potentially promote bone metastasis of lung cancer expressing its receptor CCR4. We first examined expression of chemokines by differentiating osteoclasts. CCL22 was selectively upregulated in osteoclast-like cells derived from RAW264.7 cells and mouse bone marrow cells upon stimulation with RANKL (receptor activator of nuclear factor-κB ligand). In addition, a human lung cancer cell line SBC-5 that efficiently metastasized to bone when intravenously injected into NK cell-depleted SCID mice was found to express CCR4. Stimulation of SBC-5 cells with CCL22 induced cell migration and also enhanced phosphorylation of protein kinase B/Akt and extracellular signal-regulated kinase (ERK). Furthermore, immunohistochemical analysis of bone metastasis lesions demonstrated close co-localization of tartrate-resistant alkaline phosphatase (TRAP)-positive osteoclasts expressing CCL22 and SBC-5 cells expressing CCR4. Collectively, these results suggest that osteoclasts may promote bone metastasis of cancer cells expressing CCR4 in the bone marrow by producing its ligand CCL22.This study was supported in part by a Grant-in-Aid for Young Scientists (B) (No. 15790089), Grant-in-Aids for Cancer Research (No. 16022224 and 16023225) and a Grant-in-Aid for the 21st Century COE Program from Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan, and by Solution Oriented Research for Science (SORST) of Japan Science and Technology Corporation (JST) and High-Tech Research Center Project for Private Universities: matching fund subsidy from MEXT, 2002–2006.     

The effect of repeated cryopreservation and thawing using cryotip on the clinical outcomes of embryos

PurposeTo compare the clinical outcomes of embryo transfers that were cryopreserved and thawed two or three times with those cryopreserved and thawed once by CryoTip.MethodsData for 388 single cryopreserved‐thawed blastocyst transfer cycles, performed from April 2012 to March 2014, were assessed. The blastocysts were classified into three groups: blastocysts (A) cryopreserved once, (B) cryopreserved twice, and (C) cryopreserved three times.ResultsThe pregnancy rate was 43.8% (134/306) in group A and 46.3% (38/82) in group B, while the miscarriage rate was 29.1% (39/134) in group A and 23.7% (9/38) in group B. The rate of improvement/maintenance of blastocyst grade was 84.0% (257/306) in group A and 80.5% (66/82) in group B. The pregnancy and miscarriage rates of the blastocysts that showed improvement/maintenance in the grade were 45.9% (118/257) and 29.7% (35/118) in group A and 48.5% (32/66) and 21.9% (7/32) in group B, respectively. The pregnancy rate was 33.3% (2/6), while the miscarriage rate was 0.0% (0/2) in group C.ConclusionsPregnancy rates achieved with re‐cryopreserved and rethawed blastocyst transfer were comparable to those achieved with single cryopreserved‐thawed blastocyst transfer.     

Chronic α1 blockade in a patient with Eisenmenger syndromeblockade in a patient with Eisenmenger syndrome

Summary In an 18-year-old male with Eisenmenger syndrome cyanosis and erythrocytosis were increasing. The erythrocytosis diminished following oral bunazosin and phlebotomy was not needed during the treatment. When bunazosin was stopped, the erythrocytosis increased, but when it was resumed, the erythrocytosis and general fatigue diminished.     

Real-time imaging of green fluorescent protein-tagged beta 2-adrenergic receptor distribution in living cells

In an attempt to investigate the subcellular trafficking of beta(2)-adrenergic receptor (beta(2)AR) in living cells, we performed real-time imaging of beta(2)AR tagged with green fluorescent protein (GFP). We transiently transfected a chimera construct of beta(2)AR and GFP (beta(2)AR-GFP) into HEK 293 cells, primary cultured rat hippocampal neurons and cortical neuronal cells, and then compared the dynamic changes in subcellular localization of beta(2)AR-GFP in these live cells. In the absence of ligands, beta(2)AR-GFP fluorescence was detected predominantly on the plasma membrane in HEK 293 cells as well as on the surface of cell somata and dendrites in cortical neuronal cells. In contrast, in hippocampal neurons, beta(2)AR-GFP was diffusely distributed not only on the surface of cells but in the whole cell somata and dendrites. In HEK 293 cells, cortical neuronal cells and cortical glial cells, time-lapse images showed the rapid appearance of a punctate distribution pattern that became more numerous over the 15-min course of agonist exposure. Semiquantitative analysis revealed the time-course internalization of beta(2)AR-GFP in a single living cell. In hippocampal neurons, beta(2)AR-GFP distribution became scattered both in cell somata and dendrites following agonist exposure. Three-dimensional analysis of time-lapse images revealed a significant portion of beta(2)AR-GFP was distributed in endosomal compartments, along with Alexa 546-labeled transferrin, in all types of cells. Our results demonstrate spatial and temporal redistribution pattern of beta(2)AR in living non-neuronal cells and neuronal cells.     

Overexpression of beta 1,4N-acetylgalactosaminyl- transferase mRNA as a molecular marker for various types of cancers

OBJECTIVE: To determine GalNAcT mRNA expression in human carcinoma cell lines and primary tumor tissues. Assessment of the potential use of GalNAcT mRNA as a molecular marker for detection of metastatic cancer cells in the peripheral blood of patients with hepatocellular carcinoma. METHODS/RESULTS: We investigated GalNAcT mRNA expression in various human cancer cell lines and primary cancer tissues using RT-PCR assay for GalNAcT mRNA. The expression of GalNAcT mRNA was detected in 25 of 26 cancer cell lines tested and in the majority of primary tumors from different organs: 8 of 10 colon cancers, 9 of 9 breast cancers, 11 of 12 esophageal cancers, 14 of 14 gastric cancers, 4 of 18 pancreatic cancers, 6 of 12 biliary tract cancers, 17 of 18 hepatocellular carcinomas and 13 of 14 lung cancers. Semi-quantitative analysis with duplex RT-PCR showed that the amount of the GalNAcT mRNA was enhanced in cancer tissues as compared to the surrounding cancer-free tissues. Blood specimens of 5 of 14 patients with hepatocellular carcinoma were positive for GalNAcT mRNA, all of whom developed recurrent disease in less than 24 months. Peripheral blood samples of 30 normal subjects were negative for GalNAcT mRNA. CONCLUSION: Our results suggest that the RT-PCR assay for GalNAcT mRNA could be a potentially useful molecular marker for detecting cancer dissemination in blood circulation of patients with malignancy.