Defunctioning loop ileostomy with low anterior resection for distal rectal cancer: should we make an ileostomy as a routine procedure? A prospective randomized study.

BACKGROUND/AIMS: Anastomotic leakage is a major problem in colorectal surgery particularly in low rectal cancer. The defunctioning loop ileostomy was introduced as a technique to create a manageable stoma that would divert the fecal stream from a more distal anastomosis in order to reduce the consequences of any anastomotic leakage. Therefore, the use of a defunctioning stoma has been suggested, but limited data exist to clearly determine the necessity of routine diversion. This study was designed to evaluate early morbidity, mortality and hospital stay in patients undergoing lower rectal cancer surgery concerned with or without loop ileostomy. METHODOLOGY: This is a prospective randomized study that was performed between May 2001 and March 2008. There were 256 patients who underwent elective low anterior resection and stapler anastomosis. They were divided into two groups. Group A consisted of 120 patients who underwent straight anastomosis without ileostomy and group B consisted of 136 patients who underwent straight anastomosis with loop ileostomy. Data regarding patient demographics, underlying pathology, anastomotic problems, and ileostomy-related problems were gathered. The patients were all monitored closely after surgery for an anastomotic leak and all stoma-related complications were recorded. Inclusion criteria consisted of biopsy proven adenocarcinoma of the rectum located at < or = 5 cm above the anal verge, age > or = 22 years, and informed consent. Exclusion criteria included age more than 90 years, associated co morbid conditions Stage IV with disease spread to liver and peritoneum. RESULTS: Indications for surgery were lower rectal cancer (n=256). Mean age 55.5 years (range 22-90 years) and a male: female ratio of 1.1:1. All patients were undergoing elective surgery for lower rectal cancer. In our study 12 patients in group A developed anastomotic leak, two of them were re-explored for anastomotic leak and Hartman's colostomy was carried out. There were two deaths in Group A. In group B anastomotic leak was seen in three patients. In all three, anastomotic healing took place at a later period of time on the 18th, 20th, and 25th postoperative day respectively without any additional morbidity and mortality. Ileostomy-related problems were minor and limited to the stoma and complaints requiring stoma nurse evaluation (n=8), dehydration requiring outpatient care (n=3), bleeding at the stoma closure site (n=l). No stoma site hernias have been identified so far. CONCLUSIONS: The use of defunctioning loop ileostomy in all patients undergoing lower rectal surgery with stapler anastomosis is beneficial and safe. Defunctioning loop ileostomy use has resulted in no anastomotic leak rate and considerable low morbidity. So according to our study, we strongly recommend defunctioning loop ileostomy as a routine procedure in patients undergoing lower rectal cancer surgery.

[Surgical angioplasty of isolated left coronary ostial stenosis].

A 42-year-old female had suffered from chest pain for approximately 1 month, and was admitted with unstable angina pectoris. Emergent coronary angiography showed an isolated 75% stenosis of the left coronary ostium. Repair of ostial stenosis by vein patch angioplasty was done by the transactional superior approach. Postoperative catheterization revealed an expanded left coronary orifice and the patient was discharged without any complications. We have experienced 2 other patients of isolated left coronary ostial stenosis, who had undergone double coronary artery bypass grafting. Long-term coronary angiography showed regression of ostial stenosis in 1 patient, and no progression of new lesions in either. These results suggest that direct vein patch angioplasty of the ostial lesion is an alternative procedure for isolated left coronary ostial stenosis.

Phosphatidylethanolamine deficiency in membrane lipids inhibits keratinocyte intercellular networks formation.

Ethanolamine (Etn) is required for the growth of epithelial cells in culture. Without Etn, the amount of phosphatidylethanolamine (PE) in membrane lipids is reduced, and cell proliferation stops. When the membrane lipids are deficient of PE, some extracellular signaling processes become impaired. In this study, we examined the effect of Etn deprivation on the formation of intercellular networks in immortalized human oral keratinocytes. Keratinocytes proliferate with undifferentiated morphologies in a low-calcium medium, whereas they undergo differentiation to form intercellular networks in a high-calcium medium. The cells were first cultured with or without Etn supplement in a low-calcium (0.07 mM) medium, and then the calcium concentration was raised to 1.8 mM. The localization and organization of the following proteins were examined: (1) desmogleins and plakoglobin in desmosomes, (2) E-cadherin and beta-catenin in adherens junctions and (3) actin and keratin filaments in cytoskeletons. As expected, in the Etn-supplemented cells, the elevated level of calcium induced the junctional localization of the proteins associated with desmosomes and adherens junctions and also induced the formation of keratin and actin networks. On the contrary, in the Etn-deprived cells, the elevated level of calcium induced none of the above processes. The results suggest that having a sufficient amount of PE or proper phospholipid composition in the membranes is crucial for differentiation in epithelial cells.

[Clinical evaluation of right gastroepiploic artery (RGEA) graft--comparison of RGEA with right internal thoracic artery (RITA) graft in the coronary bypass grafting (CABG) operation using only arterial grafts].

From January, 1990 through May, 1997, 100 CABG operations were conducted using only double arterial grafts. RITA/left internal thoracic artery (LITA) (n = 38) and RGEA/LITA (n = 62) groups were compared. The incidence of left main trunk lesion was higher in the RITA/LITA group (29%: 13%), and old myocardial infarction was greater in RGEA/LITA group (77%: 55%). Mean age in the RGEA/LITA group showed high tendency (66.8 +/- 8.5: 63.9 +/- 9.2). Both groups were essentially the same with respect to sex, poor left ventricular function, pre-operative aortic baloon pumping (IABP), diabetes mellitus, hypertension, cerevral vascular disease, hyperlipidemia, smoking, pre-operative ejection fraction (EF). Focal skin infection (32%: 6%) and total operative field infection (focal skin infection + mediastinitis) (39%: 8%) were higher in the RITA/LITA group. Operation time (443 +/- 81: 405 +/- 114) and pleural effusion (29%: 15%) showed high tendency in the RGEA/LITA group. Extracorporeal circulation time, aorta cross-clamping time, reoperation due to bleeding, reoperation due to mediastinitis, post-operative IABP, and post-operative EF were the same for the two groups. The difference of survival rate and cardiac event-free rate between two groups were not recognized. The RGEA/LITA group showed lower complication and similar survival rates than the RITA/LITA group. Based on the present results. RGEA may be considered more usefull than RITA.

[A case report of pre-operative simultaneous angiography of the LITA and LAD for MIDCAB surgery].

The patient was 59-year-old man, who had a 90% stenotic lesion of LAD (seg 6, just proximal). We performed minimally invasive direct coronary artery bypass (MIDCAB) surgery. At preoperative angiography, we took a photo of the posteroanterior view which is equivalent to position of an operation. Also, photos of the LITA and LAD were taken simultaneously. This simultaneous angiography was useful for deciding on the skin incision line. During the postoperative angiography, it was recognized that the skin incision line existed at the middle of the LITA and anastomotic point. In MIDCAB surgery, to obtain a good operative view could have an influence on the difficulty of the operation and effect the results of the operation. Therefore, our new angiographic technique is though to be useful for new surgical technique (MIDCAB).

[Assessment of right gastroepiploic artery grafts by thallium scintigraphy].

From 1990 to 1996 we performed coronary artery bypass grafting using only arterial grafts. Both pre- and post-operative thallium-201 exercise myocardial scintigraphy were evaluated in 68 cases (161 grafts). The rate of improvement (%) was defined as follows: (number that showed improvement of perfusion of thallium on post-operative scintigraphy/number that showed decreased perfusion of thallium on pre-operative scintigraphy) x 100. Examination was made separately regarding cases of ischemia (102 grafts) and infarction (54 grafts). For ischemic cases, the rate of improvement using left internal thoracic artery (LITA), right internal thoracic artery (RITA) and right gastroepiploic artery (RGEA) was 80% (12/15), 70% (7/10) and 71% (5/7) respectively. For infarction cases, the rate of improvement using LITA, RITA and RGEA was 54% (7/13), 60% (6/10) and 53% (9/17) respectively. Among these three groups no significant differences were noted. As a result, RGEA is thought to have usefulness equivalent to LITA and RITA.

[Urgent coronary artery bypass surgery by only arterial graft for acute myocardial infarction].

The authors conducted urgent coronary artery bypass grafting (CABG) using only arterial graft for mild and moderate acute myocardial infarction (AMI) in 9 cases from January, 1995 through December, 1996. Mild and moderate AMI means free from cardiogenic shock by catecholamines alone or catecholamines and intra aortic balloon pumping (IABP). The period from the onset of AMI to admission was 2-24 (average 8 +/- 6) hours. Coronary arteriography (CAG) was performed immediately following admission. CABG was done immediately after CAG. CPK-MB on admission was 14-184 (average 67 +/- 61) IU/l. Three cases were main trunk disease over 90% stenosis, three cases were main trunk disease equivalent if another stenotic lesion over 99% were occluded, three cases would fall into cardiogenic shock if another stenotic lesion over 99% were occluded. Postoperative IABP was necessary for three cases. No case required repetition of IABP. For minimal operation time and to attain high graft flow, saphenous vein (SV) graft are generally used for emergencies. CABG was conducted here using only arterial graft (Mean anastomosis number was 2.3). There were 8 RITA grafts, 9 LITA grafts, and 4 RGEA grafts. Post operative CAG showed all the grafts to be patent, but string sign was noted for two LITA grafts. Prognosis was favorable in all cases. We could conduct urgent CABG surgery safely for mild and moderate AMI using only arterial grafts.

[Debakey IIIb aortic dissection from a distal arch atherosclerotic aneurysm--a case report].

We treated a 75-year-old male patient with DeBakey IIIb aortic dissection from a distal arch atherosclerotic aneurysm 75 mm in diameter. Arch replacement was carried out by separate extracorporeal circulation. The entry located juxta-atherosclerotic aneurysm. It was considered that shear stress at the turning point of blood flow would occur the dissection. The relationship between the atherosclerotic aneurysm and the aortic dissection was studied.

[Two cases of CABG operation using only arterial grafts for hypothyroidism patients].

CABG operation was conducted using only arterial grafts for patients with hypothyroidism. Case 1 was a 75-year-old woman in a hypothyroid state following radioactive iodine therapy for Basedow's disease. I're-operative thyroid function could not be corrected. CABG (RITA-->#7, LITA-->#14, RGEA-->#3) was thus carried out. The post-operative course was slightly unstable. Transient conduction disturbance appeared. Case 2 was a 57-year-old man with primary hypothyroidism. Pre-operative thyroid function could be corrected, and CABG (LITA-->#7, RITA-->#9, RGEA-->#4 PD) was carried out, the post-operative course was very good. CABG with only arterial graft was thus concluded applicable to the patients with hypothyroidism.

Biotransformation of glyceryl trinitrate and elevation of cyclic GMP precede glyceryl trinitrate-induced vasodilation.

In this study, we examined glyceryl trinitrate (GTN) biotransformation and cyclic GMP elevation in vascular smooth muscle before onset of GTN-induced relaxation. Isolated rabbit aortic strips (RAS) and strips of bovine pulmonary artery (BPA) and bovine pulmonary vein (BPV) were contracted submaximally and incubated with [3H]GTN. Before onset of GTN-induced vasodilation, the tissues were freeze-clamped and then analyzed for GTN, glyceryl-1,2-dinitrate (1,2-GDN), and glyceryl-1,3-dinitrate (1,3-GDN) and for cyclic GMP. Before onset of relaxation of RAS, BPA, and BPV, there was significant biotransformation of GTN to GDN and significant elevation of cyclic GMP. There was significantly greater biotransformation of GTN and elevation of cyclic GMP by BPV than by BPA incubated with the same concentration of GTN, which was temporally related with the more rapid onset of relaxation induced in BPV than in BPA. These results are consistent with the hypothesis that the magnitude of GTN biotransformation before vasodilation is the important determinant of subsequent tissue relaxation. In GTN biotransformation before vasodilation, there was preferential formation of 1,2-GDN. These data indicate that the mechanism of GTN biotransformation to 1,2-GDN is related to elevation of cyclic GMP and subsequent vasodilation.

Relationship between biotransformation of glyceryl trinitrate and cyclic GMP accumulation in various cultured cell lines.

We assessed glyceryl trinitrate (GTN) biotransformation and cyclic GMP accumulation in cultured rat lung fibroblasts (RLF), porcine kidney epithelial (PK1), bovine aortic endothelial (BAE) and bovine aortic smooth muscle (BASM) cells. Biotransformation of 0.1 microM GTN was linear over 30 min and the percentage of glyceryl dinitrate (GDN)/10(6) cells for BAE, BASM, RLF and PK1 at 30 min was 3.1, 2.3, 5.8 and 21.7%, respectively. At low GTN concentration (0.01-0.1 microM) there was a highly selective formation of 1,2-GDN, whereas at higher GTN concentration (greater than 1 microM) this selectivity was lost. Cyclic GMP accumulation did not occur in BAE or BASM at any GTN concentration, whereas for RLF and PK1 it was highly correlated to the rate of GDN formation. Upon re-exposure to GTN after treatment of RLF or PK1 cells for 3 hr with 0.1 mM GTN, there was an almost complete loss of the cyclic GMP response, GTN biotransformation was attenuated markedly and the selective formation of 1,2-GDN at low GTN concentration was absent. However, when GTN-treated cells were incubated for 18 hr in GTN-free media, there was a recovery of the cyclic GMP response, GTN biotransformation and selective 1,2-GDN formation toward control values.(ABSTRACT TRUNCATED AT 250 WORDS)

The role of nitric oxide formation in organic nitrate-induced vasodilation and organic nitrate tolerance.

Isolated rabbit aortic strips (RAS) were contracted submaximally with phenylephrine (PE) and then were incubated with 6.2 x 10(-7) M [3H] glyceryl trinitrate (GTN) (9.98 Ci/mmol) in a 30-s time-course study. GTN-induced relaxation of RAS was monitored and tissue GTN and GDN concentrations were determined by thin-layer chromatography and liquid scintillation spectrometry. There was time-dependent biotransformation of GTN to glyceryl dinitrate (GDN) by the RAS and a time-dependent increase in cyclic GMP content in the RAS. Statistically significant (P less than 0.05) biotransformation of GTN and elevation of cyclic GMP content in the tissue were found at 10 s in RAS, whereas the onset of relaxation occurred at 12 s. During the tissue biotransformation of GTN, there was preferential formation of 1,2-GDN compared with 1,3-GDN, suggesting that it is during the process of conversion of GTN to 1,2-GDN that elevation of cyclic GMP content occurs. The results of this study are consistent with the hypothesis that GTN is a prodrug, such that biotransformation to the active metabolite, nitric oxide (NO), is involved in GTN-induced relaxation of vascular smooth muscle. The data also indicate that the mechanism of GTN biotransformation and GTN-induced activation of guanylate cyclase may be related intimately. Isolated RAS were made tolerant to organic nitrates in vitro by incubation with 5 x 10(-4) M GTN for 1 h. After washout and submaximal contraction with PE, the tissues were incubated with 5 x 10(-7) M [14C]GTN for 2 min.(ABSTRACT TRUNCATED AT 250 WORDS)

A facile, reliable method for staining blood vessel endothelium.

A modification of the silver-based stain for outlining endothelial cell borders of rabbit aorta is described. The present method uses ammonium sulfide in place of exposure to light to develop the stain. Rabbit aortic rings were sequentially immersed in 280 mM dextrose, 15 mM silver nitrate, 280 mM dextrose, dilute ammonium sulfide, and 280 mM dextrose solutions. They were then cut open and mounted on microscope slides with glycerin jelly. The procedure is rapid, easily mastered, and suited for use in most pharmacology laboratories. The resulting preparations can be viewed under reflected or transmitted light.

Mechanism of glyceryl trinitrate-induced vasodilation. II. Lack of evidence for specific binding of GTN to bovine pulmonary vein.

Radioligand binding studies were conducted to test the hypothesis that specific receptor sites for glyceryl trinitrate (GTN) exist in vascular smooth muscle. The radioligand, [3H]GTN (9.98 Ci/mmol), was incubated with whole homogenate or subcellular fractions (10,000 X g pellet, 100,000 X g pellet and 100,000 X g supernatant) of bovine pulmonary vein (BPV) at 4 degrees C, 37 degrees C or room temperature. After incubation for 5, 15, 30 or 60 min, unbound and bound ligand were estimated by physical separation and liquid scintillation spectrometry. Separation of bound from free ligand was accomplished by vacuum filtration, centrifugation, equilibrium dialysis, gel filtration or precipitation. No evidence of specific binding of [3H]GTN to BPV whole homogenate or any subcellular fraction was observed. The viability of the BPV preparations was verified by demonstrating specific binding of [3H]nitrendipine to the 100,000 X g pellet. To ensure that the ligand was present throughout the incubation procedure in sufficient concentration to detect specific binding, the ability of BPV whole homogenate and subcellular fractions to biotransform GTN to glyceryl dinitrate was measured. After 60-min incubation at 37 degrees C, greater than 95% of the GTN added was unaltered; at 90 min, more than 83% of the radioactivity was associated with GTN. Our data are interpreted as not supporting the concept of a GTN receptor in BPV.

Mechanism of glyceryl trinitrate-induced vasodilation. I. Relationship between drug biotransformation, tissue cyclic GMP elevation and relaxation of rabbit aorta.

This study was conducted to test the hypothesis that biotransformation of glyceryl trinitrate (GTN) is involved in GTN-induced relaxation of vascular smooth muscle. The temporal relationship between GTN biotransformation, elevation of cyclic GMP content and vasodilation in rabbit aortic strips (RAS) was determined. Isolated RAS were contracted submaximally with phenylephrine, and then were incubated with 0.62 microM [3H]GTN in a 30-sec time course study. GTN-induced relaxation (inhibition of phenylephrine-induced tone) of RAS was monitored; tissue cyclic GMP content was measured by radioimmunoassay; and GTN, glyceryl-1,2-dinitrate (1,2-GDN) and glyceryl-1,3-dinitrate (1,3-GDN) concentrations in RAS were measured by thin-layer chromatography and liquid scintillation spectrometry. There was time-dependent biotransformation of GTN to GDN by the RAS and a time-dependent increase in cyclic GMP content in the RAS. Statistically significant (P less than .05) biotransformation of GTN and elevation of cyclic GMP content in the tissue occurred at 10 sec, whereas the onset of GTN-induced relaxation of RAS occurred at 12 sec. During the tissue biotransformation of GTN, there was preferential formation of 1,2-GDN compared with 1,3-GDN, with 1,2-GDN/1,3-GDN ratio of 3.0/1 at 10 sec, 5.3/1 at 20 sec and 5.8/1 at 30 sec. The results of this study are consistent with the hypothesis that GTN is a prodrug, such that biotransformation to an active metabolite is involved in GTN-induced relaxation of vascular smooth muscle. The data also indicate that the mechanisms of GTN biotransformation and GTN-induced activation of guanylate cyclase may be related intimately.

A comparative study of glyceryl trinitrate biotransformation and glyceryl trinitrate induced relaxation in bovine pulmonary artery and vein.

Recent evidence supports the hypothesis that the mechanism by which glyceryl trinitrate induces relaxation of vascular smooth muscle involves the biotransformation of glyceryl trinitrate. This study was conducted to determine if there was a direct correlation between the capacity of vascular smooth muscle preparations to biotransform glyceryl trinitrate and their sensitivity to the relaxant effect of this organic nitrate. Isolated bovine pulmonary arteries and veins were contracted submaximally and cumulative dose-response relationships to glyceryl trinitrate were obtained; the vein was approximately 10 times more sensitive than the artery to glyceryl trinitrate induced relaxation. In a separate series of experiments, these vascular tissues were contracted submaximally and incubated with 0.5 microM [14C]glyceryl trinitrate for 2 min, during which glyceryl trinitrate induced relaxation was monitored. At 2 min, tissue samples were taken for determination of glyceryl trinitrate and glyceryl-1,2- and 1,3-dinitrate content by thin-layer chromatography and liquid scintillation spectrometry. Biotransformation of glyceryl trinitrate to glyceryl dinitrate occurred concomitantly with relaxation of these blood vessels. The concentration of glyceryl dinitrate in the vein was significantly less than that in the artery (p less than or equal to 0.05), even though significantly greater relaxation of the vein than the artery was observed (p less than or equal to 0.05). From these data, a simple linear relationship between glyceryl trinitrate biotransformation and relaxation is not apparent.

Cryopreservation of primary neurons for tissue culture.

We have developed new cryopreservation methods which allow storage of fetal rat central nervous system tissues for more than 1 week at 3-8 degrees C or for several months at -70 or -90 degrees C prior to tissue culture. For refrigeration, small brain regions (less than 2 mm thick) were placed intact into 35 mm petri dishes of 'hibernation medium' inside a humidified chamber. Optimal preservation was obtained with hibernation media of pH 6.8-7.4, containing 30-70 mM K+, 10-30 mM Na+, 5-50 mM PO4(2-), 20 mM lactic acid, 5 mM glucose, and less than 0.1 mM Ca2+. The media were made approximately isotonic by addition of sorbitol. For freezing, brain tissues were dissociated by gentle trituration (without enzymes) in the above medium supplemented with 5-10% dimethylsulfoxide. After refrigeration or freezing, neurons were very sensitive to damage from mechanical stress (e.g. centrifugation, harsh rinsing or trituration). Rapid changes in osmotic pressure or excessive polylysine on the tissue culture substratum also reduced neuronal survival after cryopreservation. Pretreatment of tissue culture substrata with media from lung cell cultures, or plating of neurons at higher density (2000 cells/mm2) improved neuronal survival after cryopreservation.