Intra-corporeal robot-assisted versus open radical cystectomy: a propensity score-matched analysis comparing perioperative and long-term survival outcomes and recurrence patterns

International Journal of Clinical Oncology - To compare perioperative and long-term oncological outcomes and recurrence patterns between robot-assisted radical cystectomy with intra-corporeal...     

MAdCAM-1 targeting strategy can prevent colitic cancer carcinogenesis and progression via suppression of immune cell infiltration and inflammatory signals

Chronic inflammation caused by infiltrating immune cells can promote colitis-associated dysplasia/colitic cancer in ulcerative colitis (UC) by activating inflammatory cytokine signalling through the IL-6/p-STAT3 and TNFα/NF-κB pathways. Mucosal addressin cell adhesion molecule-1 (MAdCAM-1) expressed on high endothelial venules promotes the migration of immune cells from the bloodstream to the gut via interaction with α4β7 integrin expressed on the immune cells. MAdCAM-1, has therefore drawn interest as a novel therapeutic target for treating active UC. However, the role of MAdCAM-1-positive endothelial cells in immune cell infiltration in dysplasia/colitic cancers remains unclear. We evaluated the expression of MAdCAM-1, CD31 and immune cell markers (CD8, CD68, CD163 and FOXP3) in samples surgically resected from 11 UC patients with dysplasia/colitic cancer and 17 patients with sporadic colorectal cancer (SCRC), using immunohistochemical staining. We used an azoxymethane/dextran sodium sulphate mouse model (AOM/DSS mouse) to evaluate whether dysplasia/colitic cancer could be suppressed with an anti-MAdCAM-1 blocking antibody by preventing immune cell infiltration. The number of MAdCAM-1-positive vessels and infiltrating CD8⁺, CD68⁺ and CD163⁺ immune cells was significantly higher in dysplasia/colitic cancer than in normal, SCRC and UC mucosa. In AOM/DSS mice, the anti-MAdCAM-1 antibody reduced the number, mean diameter, depth of tumours, Ki67 positivity, number of CD8⁺, CD68⁺ and CD163⁺ immune cells and the IL-6/p-STAT3 and TNF-α/NF-κB signalling. Our results indicate that targeting MAdCAM-1 is a promising strategy for controlling not only UC severity but also carcinogenesis and tumour progression by regulating inflammation/immune cell infiltration in patients with UC.     

Management of myocardial damage in muscular dystrophy

Heart failure (HF) is a fatal complication in many muscular dystrophy cases and has become the most common cause of death in Duchenne muscular dystrophy (DMD) since 2001. HF deaths in DMD occur in young patients and increase, along with respiratory failure, in older patients. Managing HF, therefore, is the most important component of DMD treatment. Management of HF is necessary in DMD patients of all ages because myocardial damage progresses regardless of age and disability. Electrocardiography, echocardiography, myocardial single-photon emission computed tomography (SPECT), and natriuretic peptides are used for the diagnosis of myocardial damage and chronic HF. Tissue Doppler echocardiography is in particularly useful for early detection of minute myocardial damage and dysfunction in DMD. The first-line drugs for chronic HF are angiotensin-converting enzyme inhibitors, and the prognosis of DMD patients has been improved using these drugs and beta-blockers. Diuretics are added in the presence of pulmonary congestion. Digoxin is most effective at a blood level of 0.5-0.8 ng/mL because of its pharmacokinetics in DMD. Surgical treatment may be necessary in cases of intractable HF. Cardiac resynchronization therapy (biventricular pacing), a treatment with an artificial pacemaker, is indicated for cases that meet specific criteria, including HF with ventricular dyssynchrony. Applications of partial left ventriculectomy (Batista procedure) and left ventricular assist devices in muscular dystrophy are likely in the near future.     

An Immunohistochemical Analysis of Implanted Woven Dacron and Expanded Polytetrafluoroethylene Grafts in Humans

Abstract: An immunohistochemical analysis was performed to clarify the healing process in implanted vascular grafts in human. Eight woven Dacron grafts and 6 expanded polytetrafluoroethylene grafts were obtained following redo surgery, limb amputation, and autopsy. The implantation periods ranged from 5 days to 148 months. The antibodies used for the analysis were specific to a-actin (smooth muscle cells), macrophages, von Willebrand factor (endothelial cells), fibrin, elastin, collagen types 1–5, CD3 (T cells), and CD20 (B cells). At 5 and 24 days after implantation, thrombi containing red blood cells and fibrin covered the anastomotic lines and some of the luminal surfaces of the grafts. Macrophages were scattered throughout the thrombi. At 11–148 months after implantation, either a single layer of endothelial cells or a thin layer of fibrin covered the anastomotic segments of the grafts, and smooth muscle cells and collagen fibers were seen forming anastomotic intimal hyperplasia (AIH). The AIH in the grafts at 94 and 148 months after implantation was almost the same thickness and length as that in the grafts at 11–36 months after implantation. Apart from the anastomotic segments, a connective tissue matrix containing collagen fibers covered the luminal surfaces, and some thrombi were noted. Most of the collagen present was type 3, in addition to some type 1, 4, and 5 collagen. No type 2 collagen was noted. Some elastin was also detected in the AIH but not in the midportion of the grafts. Some macrophages and T cells were noted in the perigraft tissues.     

Combined hepatocellular carcinoma and osteoclast-like giant cell tumor of the liver: Possible clue to histogenesis

Hepatic giant cell tumor is extremely rare, and only five cases have been reported of overt hepatocellular carcinoma, thus its histogenesis is controversial. Herein is reported a case of simultaneous hepatocellular carcinoma and osteoclast-like giant cell tumor in a single tumor. A liver tumor was found in a 74-year-old woman. Histologically the tumor consisted of two distinct components: mononuclear and multinuclear giant cells with osteoclastic giant cells, and a conventional hepatocellular carcinoma. The boundary between the two components showed transitional features. Immunohistochemistry showed that the osteoclast-like giant cells were CD68 and vimentin positive, but cytokeratin and AFP negative, while spindle-shaped cells were positive only for vimentin. In a portion of the hepatocellular carcinoma the cells were cytokeratin-8 and AFP positive. Ki-67 positivity was 10% for the hepatocellular carcinoma, 60% for the spindle-shaped cells, and 0% for the giant cells. It is possible that the tumor might have had a hepatocellular carcinoma origin, given the more highly proliferative sarcomatous changes and reactive osteoclast-like cells. This case provides a clue to the histogenesis of hepatic giant cell tumors.     

Tryptophan 2,3-dioxygenase in tumor cells is associated with resistance to immunotherapy in renal cell carcinoma

Indoleamine 2,3-dioxygenase 1 (IDO1) is a key enzyme associated with immunomodulation through its regulation of the tryptophan-kynurenine (Kyn) pathway in advanced cancers, including metastatic renal cell carcinoma (mRCC). However, the failure of IDO1 inhibitors when used in combination with immune checkpoint inhibitors (ICIs), as observed in clinical trials, raises a number of questions. This study aimed to investigate the association of tryptophan 2,3-dioxygenase (TDO) and IDO1 with cancer development and resistance to immunotherapy in patients with RCC. In our analysis of RCC tissue samples, tissue Kyn levels were elevated in advanced-stage RCC and correlated well with TDO expression levels in RCC tumor cells. In patients with mRCC, TDO rather than IDO1 was expressed in RCC tumor cells, showing a strong association with Kyn expression. Furthermore, immunohistochemical staining of TDO was strongly associated with the staining intensity of forkhead box P3, as well as ICI therapy response and survival in patients with mRCC. Our study is the first to show that TDO expression in tumor tissues is associated with progression and survival, confirming its potential as a predictive biomarker of primary resistance to immunotherapy in patients with mRCC. Our findings suggest that strategies aimed at inhibiting TDO, rather than IDO1, in combination with ICI therapy may aid in the control of mRCC progression.     

Facioscapulohumeral muscular dystrophy with sinus dysfunction]

We report a 47-year-old man with facioscapulohumeral muscular dystrophy (FSHD) presenting with sinus dysfunction. He became unable to roll over and stand up at the age of 42, but he could still walk. Facial muscle involvement, scapular winging, asymmetrical involvement, funnel chest, and the absence of contractures were typical of FSHD. Electrocardiogram (ECG) and cardiac echogram showed the overload of both right atrium and ventricle. On Holter ECG, transient P wave inversion and P-P interval elongation (maximally 2.4 seconds) repeatedly appeared mainly during sleep. There was no bundle branch block, atrioventricular junctional rhythm, or increase of premature ventricular beats. Vital capacity was decreased (0.62 L, 16% of the predicted value). Arterial blood gas analysis showed hypercapnia and hypoxia which aggravated during sleep (PaCO2 87.3Torr, PaO2 41.5Torr). Sleep apnea was not observed. Intracardiac ECG was not performed and he died 2 weeks later. In FSHD, sinus node dysfunction may become distinct especially in the setting of respiratory failure.