Regulation of P-selectin binding to the neutrophil P-selectin counter-receptor P-selectin glycoprotein ligand-1 by neutrophil elastase and cathepsin G

In the inflammatory response, leukocyte rolling before adhesion and transmigration through the blood vessel wall is mediated by specific cell surface adhesion receptors. Neutrophil rolling involves the interaction of P-selectin expressed on activated endothelium and its counter-receptor on neutrophils, P-selectin glycoprotein ligand-1 (PSGL-1). Here, it is reported that P-selectin binding to neutrophils is lost under conditions that cause the release of proteinases from neutrophil primary granules. Treatment of neutrophils with the purified neutrophil granule proteinases, cathepsin G and elastase, rapidly abolished their capacity to bind P-selectin. This inactivation corresponded to loss of the N-terminal domain of PSGL-1, as assessed by Western blot analysis. A loss of intact PSGL-1 protein from the surfaces of neutrophils after the induction of degranulation was also detected by Western blot analysis. Cathepsin G initially cleaved near the PSGL-1 N-terminus, whereas neutrophil elastase predominantly cleaved at a more C-terminal site within the protein mucin core. Consistent with this, cathepsin G cleaved a synthetic peptide based on the PSGL-1 N-terminus between Tyr-7/Leu-8. Under conditions producing neutrophil degranulation in incubations containing mixtures of platelets and neutrophils, the loss of PSGL-1, but not P-selectin, from platelet-neutrophil lysates was detected. Cathepsin G- or neutrophil elastase-mediated PSGL-1 proteolysis may constitute a potential autocrine mechanism for down-regulation of neutrophil adhesion to P-selectin.     

Participation of endogenous catecholamines in the regulation of left ventricular mass in progeny of hypertensive parents

To investigate whether adrenergic activity is a determinant of left ventricular hypertrophy in human hypertension, in each of 10 normotensive subjects with two hypertensive parents we have examined the relationship between changes in echocardiographic parameters of left ventricular anatomy and those in circulating catecholamine levels induced by three, 3 week periods of different sodium and potassium intakes. A high sodium-normal potassium regimen induced a significant reduction in upright plasma norepinephrine (from 599 +/- 89 to 379 +/- 45 pg/ml, p less than .01) and in posterior wall (PWT) and interventricular septal (IVST) thickness, as well as in the left ventricular mass index (LVMi). Changes in upright plasma norepinephrine concentrations correlated with those in IVST (r = .822, p less than .01) and in LVMi (r = .833, p less than .01). A low sodium-normal potassium diet resulted in increases in supine and upright plasma norepinephrine levels (from 356 +/- 44 to 488 +/- 89 pg/ml, p less than .001; and from 565 +/- 42 to 744 +/- 33 pg/ml, p less than .01) as well as increases in IVST and LVMi (from 97 +/- 7 to 107 +/- 7 g/m2, p less than .001). The changes in norepinephrine levels in supine and upright subjects correlated with changes in IVST (r = .836, p less than .01 and r = .796, p less than .01) and in LVMi (r = .931, p less than .001 and r = .947, p less than .001). No significant change in plasma catecholamine concentrations or in PWT, IVST, or LVMi was detected after a low sodium-high potassium regimen.(ABSTRACT TRUNCATED AT 250 WORDS)     

Percutaneous transluminal renal angioplasty in patients with solitary kidney

We report our experience with percutaneous transluminal angioplasty of renal arteries (PTRA) in solitary kidney patients. Our series includes 31 patients (mean age: 52 years). 7 with solitary kidney following surgical nephrectomy and 24 with functioning solitary kidney. PTR indicated in presence of stenoses ranging from 60–95 % of vessel lumen. Procedure, with 29 patients were technically successful and mean values for stenosis dropped from 77 % to 33 %. In order to assess the results technically, changes in arterial blood pressure (according to Martin's classification) and creatinine levels were considered. Of 25 followed-up patients, 13 were cured (52%), 8 improved (32%),and 4 were unchanged (16%%). Complications were observed during procedures in five patients (16. 1 % ), superimposing that of nonsolitary kidney patients. Good revasculariiation, reduction of blood pressure, preservation or even improvement of renal function and low complications, make PTRA the best procedure with solitary kidney patients.     

Laparoscopic gastrointestinal anastomoses using knotless barbed sutures are safe and reproducible: a single-center experience with 201 patients

Background

Intestinal anastomosis is a complex procedure during laparoscopy, mainly due to the difficulties knotting the sutures. Unidirectional barbed sutures have been proposed to simplify wall and mesentery closure, but the results for intestinal anastomosis are not clear. This study aimed to establish the feasibility and the safety of laparoscopic intestinal anastomosis using barbed suture.

Methods

Between June 2011 and May 2012, 15-cm-long unidirectional absorbable barbed sutures (V-Loc; Covidien, Mansfield, MA, USA) were used for all laparoscopic intestinal anastomoses: one suture for closure of intestinal openings after mechanical anastomoses and two sutures for hand-sewn anastomoses.

Results

Over a 1-year period, 201 consecutive patients required 220 laparoscopic anastomoses for gastrojejunostomy (n = 177; 172 during Roux-en-Y gastric bypass and 5 after gastrectomy), ileocolostomy (n = 15), colocolostomy (n = 1), esophagojejunostomy (n = 5), and jejunojejunostomy (n = 22; 4 after small bowel resection and 18 during gastric bypass or gastrectomy). Senior and training surgeons performed 209 closures of intestinal openings and 11 hand-sewn anastomoses. There was no conversion to usual sutures. One fistula occurred in an esophagojejunostomy and was managed conservatively. One self-limited anastomotic bleeding occurred, and no anastomotic stenosis occurred during 6 months of follow-up evaluation.

Conclusions

The use of knotless barbed suture for laparoscopic intestinal anastomosis is safe and reproducible.     

Laparoscopic Colorectal Surgery for Obese Patients: Decreased Conversions with the Hand-Assisted Technique

Background

Laparoscopic surgery benefits obese patients but technical difficulties associated with suboptimal exposure and access in these subjects may prompt conversion to open surgery. Hand-assisted laparoscopic surgery (HALS) confers advantages over standard laparoscopy (LAP) by facilitating tactile feedback, assisted dissection, and retraction. These benefits could be particularly valuable in obese patients, allowing completion of difficult laparoscopic procedures in this subgroup. Our aim was to compare intra-operative and post-operative outcomes of HALS and LAP approaches in obese patients undergoing colorectal resection at our institution.

Methods

A retrospective study of a prospectively maintained laparoscopic colorectal surgery database was performed. HALS and LAP cases performed in obese patients (body mass index (BMI)?>30) were identified and compared for the following outcomes: operative time, intra-operative complications, rate of conversion to open, blood loss, length of stay, post-operative morbidity, and mortality. Outcomes for the converted patients were included on an intention-to-treat basis for all primary analyses. A secondary analysis of nonconverted and converted cases was also performed.

Results

Over a 5-year period, 496 obese patients underwent laparoscopic colorectal resection; 86 HALS and 410 LAP cases. The two groups were comparable in terms of age, gender, BMI, and indications for surgery. Conversion to open surgery was less often necessary in HALS compared to LAP cases (3.5 % vs. 12.7 %, p?=?0.014). The LAP group had a significantly smaller incision length for specimen extraction (HALS (7.0?±?1.3 cm) vs. LAP (5.7?±?2.1 cm), p?<?0.001). Length of stay, operative time, morbidity, and mortality rates were comparable between the two groups.

Conclusion

In obese patients who require colectomy, the HALS approach increases the likelihood of a successful minimally invasive operation. At the cost of a clinically negligible increase in incision length, HALS may save a high-risk group conversion to formal laparotomy and the adverse outcomes related to this.     

Use of fenoldopam to control renal dysfunction early after liver transplantation.

With the aim of assessing whether fenoldopam can help to preserve renal function after liver transplantation, we randomized 140 consecutive recipients with comparable preoperative renal function to receive fenoldopam 0.1 microg/kg/minute (group F, 46 patients), dopamine 3 microg/kg/minute (group D, 48 patients), or placebo (group P, 46 patients) from the time of anesthesia induction to 96 hours postoperatively. There were no differences between the groups in intraoperative urinary output or furosemide administration (both P =.1). Daily recordings made during the first 4 postoperative days revealed no significant differences in urinary output (P =.1), serum creatinine (P =.5), the incidence of renal insufficiency (P =.7), the need for loop diuretics (P =.9) or vasoactive drugs (P =.8). In comparison with preoperative levels, creatinine clearance at the end of the study in the patients receiving fenoldopam remained substantially unchanged, whereas it decreased by 39 and 12.3%, respectively, in the subjects receiving placebo or dopamine (P <.001); blood cyclosporine A (CsA) levels were similar in the 3 groups (P =.1). Three subjects died in the intensive care unit (1 in each group, P =.9), 2 of them had renal failure. In conclusion, our results confirm the inefficacy of dopamine in preventing or limiting early renal dysfunction after liver transplantation, and suggest that fenoldopam may preserve creatinine clearance by counterbalancing the renal vasoconstrictive effect of CsA, as it has been reported in previous experimental studies.     

Locoregional recurrence in patients with HER2 positive breast cancer

Literature shows that HER2/neu positive breast cancer cells are more sensitive to radiation-induced apoptosis by targeting the epidermal growth factor receptor family tyrosine kinase. We selected 466 patients with pT1-2 HER2/neu positive tumors who received adjuvant trastuzumab for primary invasive breast cancer. Patients were divided into three groups [Quadrantectomy followed by conventional radiotherapy vs Quadrantectomy followed by Intra-operative radiotherapy with electrons vs Mastectomy without radiotherapy]. After a median follow-up of 52 months, the 5-year cumulative incidence of locoregional recurrence (LRR) was 1.9%, 11.5% and 5.0% respectively (p < 0.01). At the multivariate analysis, extensive perivascular invasion, Luminal B HER2/Progesterone Receptor (PgR) negative status and Quadrantectomy followed by Intra-operative radiotherapy with electrons have significantly increased the risk of LRR. Our results suggest that HER2/neu positive breast cancer might have better outcomes when treated simultaneously with external radiotherapy and trastuzumab. Moreover, we underline the importance of PgR and further new stratification of risk among luminal subtypes.     

Sentinel node mapping in high risk endometrial cancer after laparoscopic supracervical hysterectomy with morcellation

INTRODUCTIONOccult endometrial cancer after supracervical hysterectomy is very uncommon. Even if optimal management of those rare cases is still unproven, to guide the need for further therapies, restaging should be recommended in this situation.PRESENTATION OF CASEWe report of a 60-year old woman with occult high risk endometrial cancer after supracervical hysterectomy with morcellation. We describe the feasibility of laparoscopic intraoperative sentinel node identification with cervical stump removing to restage the suspicious early stage high risk endometrial cancer.DISCUSSIONIn high risk endometrial cancer surgical restaging is important, considering that 10–35% of cases can present pelvic nodal metastasis. To reduce the treatment related morbidity maintaining the benefit of surgical staging, with a negative preoperative PET/CT, we performed a laparoscopic SN mapping with cervical stump removing.CONCLUSIONThis report highlight the fact that SN mapping with cervical injection is a feasible and safe technique also without the uterine corpus after supracervical hysterectomy with morcellation.