Management of colorectal anastomotic stricture with multidiameter balloon dilation: long-term results.

BACKGROUND: Postoperative colorectal anastomotic strictures are quite common. As such, many techniques have been available to address such a problem, one of which is endoscopic dilation. The aim of the present study was to evaluate the long-term outcomes following endoscopic dilation using a multidiameter balloon. METHODS: A retrospective study was conducted on patients with postoperative anastomotic stenosis treated with endoscopic dilation using a multidiameter balloon at our institution, in January 2005-December 2019 were retrospectively reviewed, excluding those with tumor recurrence. Perioperative factors, complications, and recurrence rates were analyzed. RESULTS: There were 40 patients, (22 males and 18 females, mean age 64.6 ± 10.7 years, range 33-84 years). The median follow-up period was 56 months (interquartile range 22.5-99 months). Only 1 complication occurred, micro-perforation due to guided wire injury, which was managed conservatively. Five (12.5%) patients developed restenosis and underwent repeat balloon dilation. None of the five recurrences required more aggressive management, such as redo anastomosis. CONCLUSIONS: Endoscopic multidiameter balloon dilation is a safe and effective method for treating benign colorectal anastomotic strictures.

Targeting TYRO3 inhibits epithelial-mesenchymal transition and increases drug sensitivity in colon cancer.

Colon cancer is the third leading cause of death from cancer worldwide with less than 10% survival rate at the late stage. Although mutations of certain genes have been implicated in familial colon cancer development, the etiology of the majority of colon cancer remains unknown. Herein, we identified TYRO3 as a potential oncogene. Immunohistochemical staining results demonstrated that levels of TYRO3 were markedly elevated in polyps and colon cancer cells and were negatively correlated with prognosis. Overexpression of TYRO3 enhanced cell motility, invasion, anchorage-independent growth and metastatic ability, while knockdown of TYRO3 impaired all these processes. Results from meta-analysis showed that TYRO3 was associated with epithelial-mesenchymal transition (EMT) signatures. Gain-of-function and loss-of-function experiments demonstrated that expression of SNAI1, the master regulator of EMT, was regulated by TYRO3 and played a major role in mediating TYRO3-induced EMT processes. The murine model also demonstrated that Tyro3 and Snai1 were upregulated in the early stage of colon cancer development. To provide a proof-of-concept that TYRO3 is a druggable target in colon cancer therapy, we raised anti-TYRO3 human antibodies and showed that treatment with the human antibody abolished TYRO3-induced EMT process. More importantly, administration of this anti-TYRO3 antibody increased drug sensitivity in primary cultured colon cancer cells and xenografted mouse tumors. These findings demonstrate that TYRO3 is a novel oncogene and a druggable target in colon cancer.

Overexpression of Aurora-C interferes with the spindle checkpoint by promoting the degradation of Aurora-B.

The chromosomal passenger complex (CPC) plays a pivotal role in controlling accurate chromosome segregation and cytokinesis during cell division. Aurora-B, one of the chromosomal passenger proteins, is important for the mitotic spindle assembly checkpoint (SAC). Previous reports noted that Aurora-C is predominantly expressed in male germ cells and has the same subcellular localization as Aurora-B. Increasing evidence indicates that Aurora-C is overexpressed in many somatic cancers, although its function is uncertain. Our previous study showed that the aberrant expression of Aurora-C increases the tumorigenicity of cancer cells. Here, we demonstrate that overexpressed Aurora-C displaces the centromeric localization of CPCs, including INCENP, survivin, and Aurora-B. When cells were treated with nocodazole to turn on SAC, both the Aurora-B protein stability and kinase activity were affected by overexpressed Aurora-C. As a result, the activation of spindle checkpoint protein, BubR1, and phosphorylation of histone H3 and MCAK were also eliminated in Aurora-C-overexpressing cells. Thus, our results suggest that aberrantly expressed Aurora-C in somatic cancer cells may impair SAC by displacing the centromeric localization of CPCs.

A retrospective study of pulmonary infarction in patients with systemic lupus erythematosus from southern Taiwan.

Since large-scale reports of pulmonary infarction in systemic lupus erythematosus (SLE) are limited, a retrospective study was performed for this manifestation in 773 hospitalized patients in southern Taiwan from 1999 to 2009. Pulmonary infarction was defined as the presence of pulmonary embolism, persistent pulmonary infiltrates, and characteristic clinical symptoms. Demographic, clinical, laboratory, and radiological images data were analyzed. There were 12 patients with pulmonary embolism and 9 of them had antiphospholipid syndrome (APS). Six patients (19 to 53 years, average 38.2 ± 12.6) with 9 episodes of lung infarction were identified. All cases were APS and four episodes had coincidental venous thromboembolism. There were four episodes of bilateral infarction and seven episodes of larger central pulmonary artery embolism. Heparin therapy was routinely prescribed and thrombolytic agents were added in two episodes. Successful recovery was noted in all patients. In conclusion, there was a 0.8% incidence of pulmonary infarction in patients with SLE, all with the risk factor of APS. Differentiation between pulmonary infarction and pneumonia in lupus patients should be made; they have similar chest radiography with lung consolidation but require a different clinical approach in management. Although this report is a retrospective study with relatively small numbers of lupus patients with lung infarcts, our observation might provide beneficial information on the clinical features and radiological presentations during the disease evolution of pulmonary infarction in SLE with APS.

(S)-emopamil protects against global ischemic brain injury in rats.

(S)-Emopamil is a novel calcium channel blocker of the phenylalkylamine class, with potent serotonin S2 antagonist activity. We investigated the effect of (S)-emopamil on the histopathologic consequences of global brain ischemia in anesthetized rats. Pretreated rats (n = 15) received 20 mg/kg i.p. (S)-emopamil 30 minutes before and 2 hours following 10 minutes of bilateral common carotid artery occlusion plus arterial hypotension (50 mm Hg). Quantitative cell counts following 3 days' survival revealed a marked loss of pyramidal neurons in all subsectors of the hippocampal CA1 area of untreated ischemic rats (n = 15). In contrast, in (S)-emopamil pretreated rats numbers of normal neurons were significantly higher, by 2.4-, 1.9-, and 1.8-fold, respectively, in the medial, middle, and lateral subsectors of the CA1 area. For example, normal neuron counts in the medial CA1 subsector were 34 +/- 9 (mean +/- SEM) in untreated ischemic rats compared with 82 +/- 13 in (S)-emopamil pretreated rats (control nonischemic value [n = 5] 157 +/- 2). By semiquantitative grading, (S)-emopamil also decreased ischemic changes in the cerebral cortex. No significant effect of (S)-emopamil on ischemic injury was detected in rats treated beginning 30 minutes after the ischemic insult (n = 10). Thus, pretreatment with (S)-emopamil is beneficial in decreasing the severity of neuronal injury in global brain ischemia.