Robotic surgery for rectal cancer

Laparoscopic surgery has gained acceptance as a less invasive approach in the treatment of colon cancer. However, laparoscopic surgery for rectal cancer, particularly cancer of the lower rectum, is still challenging because of limited accessibility. Robotic surgery overcomes the limitations of laparoscopy associated with anatomy and offers certain advantages, including 3‐D imaging, dexterity and ambidextrous capability, lack of tremors, motion scaling, and a short learning curve. Robotic rectal surgery has been reported to reduce conversion rates, particularly in low anterior resection, but it is associated with longer operative times than the conventional laparoscopic approach. Postoperative morbidities are similar between the robotic and conventional laparoscopic approaches, and oncological outcomes such as the quality of the mesorectum and the status of resection margins are also equivalent. The possible superiority of robotic surgery in terms of the preservation of autonomic function has yet to be established in research based on larger numbers of patients. Although robotic rectal surgery is safe, feasible, and appears to overcome some of the technical limitations associated with conventional laparoscopic surgery, the advantages provided by this technical innovation are currently limited. To justify its expensive cost, robotic surgery is more suitable for select patients, such as obese patients, men, those with cancer of the lower rectum, and those receiving preoperative chemoradiotherapy.     

Circulating nucleated peripheral blood cells contribute to early‐phase meniscal healing

The purpose of this study was to assess how peripheral blood cells (PBCs) contribute to meniscus repair, using a parabiotic rat model. Wild‐type (WT) and green fluorescent protein (GFP) transgenic rats were conjoined at the torso. After 4 weeks, the anterior part of the medial meniscus of both groups of rats was removed. At 1, 2, 4, 8 and 12 weeks post‐meniscectomy, repaired tissue was evaluated using stereomicroscopy, histology with toluidine blue staining, and immunofluorescence microscopy. Stereomicroscopic observations and confocal laser microscopy revealed that a high number of GFP‐positive cells were present in the repaired meniscus of WT rats 1 week post‐meniscectomy, and the number of GFP‐positive cells decreased over time. Based on blood chimerism, the ratios of PBCs in the repaired meniscus were 20.5 ± 2.3% at 1 week, 8.3 ± 0.9% at 2 weeks, 4.4 ± 0.9% at 4 weeks, 2.1 ± 0.9% at 8 weeks, and 0.5 ± 0.4% at 12 weeks, post‐meniscectomy. Histologically, fibrochondrocytes were observed in the repaired meniscus of WT rats after 4 weeks, some of which were GFP‐positive. The chondrogenic marker, type II collagen, was merged within the PBCs in the repaired tissue. However, type‐II‐collagen‐positive cell ratio and metachromasia in the repaired meniscus were not equivalent in normal meniscal tissue. This indicated that PBCs were present within the repaired meniscus at an early phase, replacing the excised meniscal cells, suggesting PBCs contributed to meniscal healing. The tissue repair contribution by these cells decreased at later phases. Copyright © 2014 John Wiley & Sons, Ltd.     

Novel bis-tetrahydrofuranylurethane-containing nonpeptidic protease inhibitor (PI) UIC-94017 (TMC114) with potent activity against multi-PI-resistant human immunodeficiency virus in vitro

We designed, synthesized, and identified UIC-94017 (TMC114), a novel nonpeptidic human immunodeficiency virus type 1 (HIV-1) protease inhibitor (PI) containing a 3(R),3a(S),6a(R)-bis-tetrahydrofuranylurethane (bis-THF) and a sulfonamide isostere which is extremely potent against laboratory HIV-1 strains and primary clinical isolates (50% inhibitory concentration [IC(50)], approximately 0.003 micro M; IC(90), approximately 0.009 micro M) with minimal cytotoxicity (50% cytotoxic concentration for CD4(+) MT-2 cells, 74 micro M). UIC-94017 blocked the infectivity and replication of each of HIV-1(NL4-3) variants exposed to and selected for resistance to saquinavir, indinavir, nelfinavir, or ritonavir at concentrations up to 5 micro M (IC(50)s, 0.003 to 0.029 micro M), although it was less active against HIV-1(NL4-3) variants selected for resistance to amprenavir (IC(50), 0.22 micro M). UIC-94017 was also potent against multi-PI-resistant clinical HIV-1 variants isolated from patients who had no response to existing antiviral regimens after having received a variety of antiviral agents. Structural analyses revealed that the close contact of UIC-94017 with the main chains of the protease active-site amino acids (Asp-29 and Asp-30) is important for its potency and wide spectrum of activity against multi-PI-resistant HIV-1 variants. Considering the favorable pharmacokinetics of UIC-94017 when administered with ritonavir, the present data warrant that UIC-94017 be further developed as a potential therapeutic agent for the treatment of primary and multi-PI-resistant HIV-1 infections.     

Overexpression of matrix metalloproteinase-9 promotes intravascular thrombus formation in porcine coronary arteries in vivo

OBJECTIVE: Matrix metalloproteinases (MMPs) cause extracellular matrix degradation and may be involved in the rupture of atherosclerotic plaques by degrading fibrous cap, resulting in the intravascular thrombus formation. Here we examined whether local overexpression of MMP-9 alters the characteristics of arteriosclerotic vascular lesions and promotes thrombosis after balloon injury in porcine coronary arteries in vivo. METHODS AND RESULTS: Balloon angioplasty was performed in the left coronary arteries followed by injection of adenovirus vector solution encoding either MMP-9 or beta-galactosidase (beta-gal) gene into the injured coronary arteries. Three weeks after the gene transfer, histological examination demonstrated that macroscopic intravascular thrombus formation was noted at the MMP-9-transfected site but not at the beta-gal-transfected site. Microscopic intramural thrombus area was significantly larger at the MMP-9-transfected site as compared to the beta-gal-transfected site. Co-transfection of tissue inhibitor of metalloproteinase-1 (TIMP-1) with MMP-9 prevented the intravascular thrombus formation in vivo. Western blot analysis revealed the reduced expression of intact tissue factor pathway inhibitor-1 and the increased tissue factor (TF) expression at the MMP-9-transfected sites. CONCLUSION: These results provide the first in vivo evidence that overexpression of MMP-9 promotes intravascular thrombus formation after balloon injury due in part to the activation of TF-mediated coagulation cascade.     

Long-term outcome of hepatocellular carcinoma patients who underwent liver resection using microwave tissue coagulation

Background/Aims. Our policy for the surgical treatment of hepatocellular carcinoma (HCC) has been to minimize the extent of liver resection using a microwave tissue coagulator (MTC) and to not perform Pringle''s maneuver for the prevention of ischemic injury to the liver routinely. We verify the safety of liver resection using MTC in HCC patients with poor liver functional reserve, and clarify the long-term outcome of HCC patients who underwent curative resection using MTC. Methodology. One hundred sixty-eight patients who underwent curative resection using MTC between 1992 and 2001 were divided into two groups according each patient''s score in the Indocyanin Green Retension 15 Test (ICG-R15 test). The high (ICG-R15 values>20) and low ICG-R15 groups (ICG-R15 values<20) included 100 and 68 HCC patients, respectively. Clinical characteristics of each group were evaluated, and operative mortality and morbidity, as well as overall and disease-free survival rates, were compared between the two groups to determine risk factors for overall and disease-free survival. Results. Although there were significant differences in liver function-related parameters between the low and high ICG-R15 groups, no differences in surgical or tumor factors were found. No patients in this study developed post-operative liver failure, and there was no significant difference in morbidity between the low and high ICG-R15 groups. The overall survival rate of the low ICG-R15 group was significantly longer than the high ICG-R15 group (p=0.0003). Cox''s multivariate analysis showed that an ICG-R15 value less than 20 was the only significant independent factor for overall survival. Disease-free survival rates in the low ICG-R15 group were significantly longer than in the high ICG-R15 group (p=0.0007). Multivariate analysis showed that serum albumin level and number of tumors were significant independent factors for disease-free survival. Conclusion. The long-term outcome of HCC patients with low ICG-R15 following curative resection using MTC was acceptable. This procedure was safe even for patients with high ICG-R15.     

A case of Mycobacterium abscessus pulmonary infection; effectiveness of clarithromycin, amikacin and imipenem/cilastatin]

A 42-year-old woman presented with persistent cough, bloody sputum and fever. Her chest X-ray film showed an infiltrative shadow with cavitation in the upper lobe of the left lung. Acid-fast-bacilli were shown by sputum smear staining. The anti-tuberculosis drugs isoniazid, refampicin, ethambutol and pyrazinamide were prescribed, but her symptoms and chest X-ray findings did not improve. Findings of MTD and MAC-PCR were negative but Mycobacterium abscessus was confirmed by sputum culture with the DNA hybridization method. Combination therapy with clarithromycin, amikacin and imipenem/cilastatin for one month improved her symptoms and chest X-ray shadow, and clarithromycin monotherapy was carried out for another ten months. Drug susceptibility tests revealed this mycobacterium was sensitive to clarithromycin and amikacin. To determine the environmental factors related to this infection, several samples were examined. Acid-fast-bacilli were present in a smear from the bath room drain. However, to confirm the infectious routes, longer observation is needed. Moreover, serum amyloid protein A and ESR were useful markers to estimate the clinical course.     

Application of nanoparticle technology for the prevention of restenosis after balloon injury in rats

Restenosis after percutaneous coronary intervention continues to be a serious problem in clinical cardiology. Recent advances in nanoparticle technology have enabled us to deliver an antiproliferative drug selectively to the balloon-injured artery for a longer time. NK911, which is a core-shell nanoparticle of polyethyleneglycol-based block copolymer encapsulating doxorubicin, accumulates in vascular lesions with increased permeability. We first confirmed that balloon injury caused a marked and sustained increase in vascular permeability (as evaluated by Evans blue staining) for a week in the rat carotid artery. We then observed that intravenous administration of just 3 times of NK911, but not doxorubicin alone, significantly inhibited the neointimal formation of the rat carotid artery at 4 weeks after the injury in both a single- and double-injury model. Immunostaining demonstrated that the effect of NK911 was due to inhibition of vascular smooth muscle proliferation but not to enhancement of apoptosis or inhibition of inflammatory cell recruitment. Measurement of vascular concentrations of doxorubicin confirmed the effective delivery of the agent to the balloon-injured artery by NK911 in both a single- and double-injury model. RNA protection assay demonstrated that NK911 inhibited expression of several cytokines but not that of apoptosis-related molecules. NK911 was well tolerated without any adverse systemic effects. These results suggest that nanoparticle technology to target vascular lesions with increased permeability is a promising and safe approach for the prevention of restenosis after balloon injury. The full text of this article is available at http://www.circresaha.org.     

Mesenteric panniculitis of the colon

Eighteen cases of mesenteric panniculitis of the colon collected from the literature, together with two cases from the authors' source, were reviewed. The disease occurred most often in late adult life, with a male predominance. Symptoms were abdominal pain, diarrhea, constipation, and a lower abdominal mass in most patients. Barium enema disclosed narrowing, shortening, and poor extensibility of the colon, and ultrasonography and computed tomography showed thickening of the mesocolon and colonic wall with soft-tissue density. Exploratory laparotomy was done in all patients, and colectomy, colostomy, or other surgical treatments were performed in 17 (85 percent). Gross appearance at the time of surgery was characterized by a marked thickening or a firm mass of the mesocolon with a puckered surface involving the appendices epiploicae of the colon. Microscopically, degeneration of the adipose tissue, revealed by aggregates of lipid-laden macrophages, was diagnostic. Inflammatory infiltration and fibrosis also were present in many patients. Mesenteric panniculitis of the colon seems to be a lesion more advaced than the same condition of the small intestine, and colostomy or bypass surgery may be needed for alleviation of severe symptoms.