Angiotensin II increases parathyroid hormone-related protein (PTHrP) and the type 1 PTH/PTHrP receptor in the kidney

Angiotensin II (AngII) participates in the pathogenesis of kidney damage. Parathyroid hormone (PTH)-related protein (PTHrP), a vasodilator and mitogenic agent, is upregulated during renal injury. The aim of this study was to investigate the potential relation between AngII and PTHrP system in the kidney. Different methods were used to find that both rat mesangial and mouse tubuloepithelial cells express PTHrP and the type 1 PTH/PTHrP receptor (PTH1R). In these cells, AngII increased PTHrP mRNA and protein production. In contrast, PTH1R mRNA was increased in mesangial cells and downregulated in tubular cells, but its protein levels were unmodified in both cells. AT(1) antagonist, but not AT(2), abolished AngII effects on PTHrP/PTH1R. The in vivo effect of AngII was further investigated by systemic infusion (a low dose of 50 ng/kg per min) into normal rats. In controls, PTHrP immunostaining was mainly detected in renal tubules. In AngII-infused rats, PTHrP staining increased in renal tubules and appeared in the glomerulus and the renal vessels. After AngII infusion, PTHR1 staining was markedly increased in all these renal structures at day 3 but remained elevated only in tubules at day 7. The AT(1) antagonist, but not the AT(2), significantly diminished AngII-induced PTHrP and PTHR1 overexpression in the renal tissue, associated with a decrease in tubular damage and fibrosis. The results indicate that AngII regulates renal PTHrP/PTH1R system via AT(1) receptors. These findings demonstrate that PTHrP upregulation occurs in association with the mechanisms of AngII-induced kidney injury.     

Results of the Italian multicenter study on 239 super-obese patients treated by adjustable gastric banding

Background: Laparoscopic adjustable gastric banding (LAGB) is the most common bariatric operation. This study is a retrospective analysis of the multicenter Italian experience in patients with BMI >50 over the last 4 years. Methods: An electronic data sheet made for LAGBoperated patients since January 1996, was mailed and e-mailed to all surgeons involved in this kind of procedure in Italy. Items regarding patients with BMI >50 were selected. Analysis used Fisher's exact test and logarithmic regression analysis (P<0.05 significant). Data were expressed as mean ± SD. Results: 239 patients (13.3%), out of 1,797 LapBand^? operated patients entered the study (179F / 60M), with mean age 37.6±11.3 years (19-69) and mean BMI 54.6±4.8 (50.1-83.6). Laparotomic conversion rate was 5.4% (44/239). Postoperative complications occurred in 24 / 239 patients (9.0%). Follow-up was obtained in 218 / 218, 198 / 198, 121 / 147, 75 / 93, 30 / 38 LAGB patients at 6, 12, 24, 36, and 48 months respectively. At these time periods, mean BMI was 46.7, 43.9, 42.2, 41.9, and 39.3 kg/m². At the same intervals, mean %EWL was 24.1, 34.1, 38.8, 38.9, and 52.9%.The number of patients with <25% EWL at 12, 24, 36, and 48 months follow-up were 34, 10, 4, and 0. Serious co-morbidities (189 in 124 of 239, 57%) had completely resolved 1 year postoperatively in 74 / 124 of the patients (59.6%). Conclusion: Although super-obese patients following the LAGB remain obese with BMI >35, in the short-term most lose their co-morbidities, with a very low morbidity and mortality rate.     

Regular dilatation is unnecessary after tubularized incised-plate hypospadias repair

OBJECTIVE: To determine if patients who undergo tubularized incised-plate (TIP) urethroplasty need regular dilatation to prevent neourethral strictures or meatal stenosis. PATIENTS AND METHODS: The follow-up of two consecutive series of patients who underwent primary TIP hypospadias repair by one surgeon was reviewed. The first 72 patients (group 1) had periodic neourethral calibrations for 1 year after repair, while the next 62 patients (group 2) had no routine dilatation, except for six patients (10%) in whom the meatus appeared to be small. Urethroscopy was performed in both groups at the time of fistula repair, skin revisions or during anaesthesia for unrelated procedures. RESULTS: There was no evidence of scarring in group 1; one case of meatal stenosis and one neourethral stricture were detected in group 2. The difference in outcome was not statistically significant (P = 0.4). Overall, the incidence of meatal stenosis was low (0.7%) and comparable with most recent series in which postoperative calibration was not used routinely. CONCLUSION: Dilatation of the neourethra is unnecessary after TIP urethroplasty. Calibration or uroflowmetry 6 months after surgery may be useful to detect subclinical obstruction.     

Guidelenines in the management of obstructing cancer of the left colon: consensus conference of the world society of emergency surgery (WSES) and peritoneum and surgery (PnS) society

Background

Obstructive left colon carcinoma (OLCC) is a challenging matter in terms of obstruction release as well of oncological issues. Several options are available and no guidelines are established. The paper aims to generate evidenced based recommendations on management of OLCC.

Methods

The PubMed and Cochrane Library databases were queried for publications focusing on OLCC published prior to April 2010. A extensive retrieval, analyses, and grading of the literature was undertaken. The findings of the research were presented and largely discussed among panellist and audience at the Consensus Conference of the World Society of Emergency Surgery (WSES) and Peritoneum and Surgery (PnS) Society held in Bologna July 2010. Comparisons of techniques are presented and final committee recommendation are enounced.

Results

Hartmann's procedure should be preferred to loop colostomy (Grade 2B). Hartmann's procedure offers no survival benefit compared to segmental colonic resection with primary anastomosis (Grade 2C+); Hartmann's procedure should be considered in patients with high surgical risk (Grade 2C). Total colectomy and segmental colectomy with intraoperative colonic irrigation are associated with same mortality/morbidity, however total colectomy is associated with higher rates impaired bowel function (Grade 1A). Segmental resection and primary anastomosis either with manual decompression or intraoperative colonic irrigation are associated with same mortality/morbidity rate (Grade 1A). In palliation stent placement is associated with similar mortality/morbidity rates and shorter hospital stay (Grade 2B). Stents as a bridge to surgery seems associated with lower mortality rate, shorter hospital stay, and a lower colostomy formation rate (Grade 1B).

Conclusions

Loop colostomy and staged procedure should be adopted in case of dramatic scenario, when neoadjuvant therapy could be expected. Hartmann's procedure should be performed in case of high risk of anastomotic dehiscence. Subtotal and total colectomy should be attempted when cecal perforation or in case of synchronous colonic neoplasm. Primary resection and anastomosis with manual decompression seems the procedure of choice. Colonic stents represent the best option when skills are available. The literature power is relatively poor and the existing RCT are often not sufficiently robust in design thus, among 6 possible treatment modalities, only 2 reached the Grade A.     

Timing of Resection of Liver Metastases Synchronous to Colorectal Tumor: Proposal of Prognosis-Based Decisional Model

Background Timing of hepatectomy for synchronous metastases of colorectal cancer is still debated. The aim of this retrospective study was to analyze prognostic factors after synchronous and delayed liver resections to define selection criteria for choosing timing of hepatectomy. Methods The study was performed on 127 patients with synchronous metastases undergoing radical hepatectomy. We divided patients according to the timing of hepatectomy: 70 synchronous (group A) and 57 delayed (group B). Results Overall survival was similar between the two groups (5-year survival 30.8% vs. 32.0% A vs. B, P = .406). The multivariate analysis evidenced four independent prognostic factors in group A: male sex (P = .04), T4 (P = .0035), more than three metastases (P = .0001), and metastatic infiltration of nearby structures (P < .0001). There were no statistically significant prognostic factors in group B. Patients with more than three metastases had a significantly worse survival in group A than in group B (3-year survival, 15.0% vs. 34.3%, P = .007); similarly, borderline significant difference was encountered in patients with T4 primary tumor (3-year survival, 16.7% vs. 60%, P = .064) Conclusions Patients with liver metastases synchronous with colorectal cancer with T4 primary tumor, metastasis infiltration of neighboring structures, and especially with more than three metastases should receive neoadjuvant chemotherapy before liver resection.     

Postoperative Liver Dysfunction and Future Remnant Liver: Where Is the Limit?

Background The future remnant liver (FRL) limit for safe major hepatectomy with low risk of postoperative liver failure has not yet been well defined. Methods Between April 2000 and September 2004, every patient scheduled for major hepatectomy in our institution underwent CT-volumetry of FRL. Patients with FRL <25% underwent portal vein embolization (PVE). Exclusion criteria were PVE, associated vascular resection and liver cirrhosis. The FRL was correlated with short-term results in patients with normal liver (group A) and those with impaired liver function secondary to neoadjuvant chemotherapy or cholestasis (bilirubin >2 mg/100 ml) (group B). Liver dysfunction was defined as both PT <50% and serum bilirubin level >5 mg/100 ml for three or more consecutive days. Results A total of 119 patients were analyzed, 72 in group A and 47 in group B. The FRL value was the only significant risk factor for postoperative liver dysfunction in the univariate and multivariate analysis (p = 0.009). The FRL did not correlate with postoperative mortality and morbidity. Bilirubin and prothrombin time (PT) on days 3 and 7 were significantly correlated to FRL in both groups. In group A, patients with postoperative liver dysfunction had a FRL<30% (3 versus 0; p = 0.005). According to receiving operator characteristic (ROC) curve analysis, a FRL value of 26.5% predicted postoperative liver dysfunction with 66.7% sensitivity, 97.1% specificity, 50% positive predictive value (PPV), and 98.5% negative predictive value (NPV). In group B, patients with postoperative liver dysfunction had a FRL <35% (4 versus 0; p = 0.027). According to ROC curve analysis, a FRL value of 31.05% predicted postoperative liver dysfunction with 75% sensitivity, 79.1% specificity, 25% PPV, and 97.1% NPV. Conclusions Hepatectomy can be considered safe when FRL is >26.5% in patients with healthy liver and >31% in patients with impaired liver function.     

Parathyroid hormone regulates the distribution and osteoclastogenic potential of hematopoietic progenitors in the bone marrow

Parathyroid hormone (PTH) increases both the number of osteoclast in bone and the number of early hematopoietic stem cells (HSCs) in bone marrow. We previously characterized the phenotype of multiple populations of bone marrow cells with in vitro osteoclastogenic potential in mice. Here we examined whether intermittent administration of PTH influences these osteoclast progenitor (OCP) populations. C57BL/6 mice were treated with daily injections of bPTH(1–34) (80 µg/kg/day) for 7 or 14 days. We found that PTH caused a significant increase in the percentage of TN/CD115⁺CD117^high and TN/CD115⁺CD117^int cells (p < .05) in bone marrow on day 7. In contrast, PTH decreased the absolute number of TN/CD115⁺CD117^low cells by 39% on day 7 (p < .05). On day 14, there was no effect of PTH on osteoclast progenitor distribution in vivo. However, PTH treatment for 7 and 14 days did increase receptor activator of NF‐κB ligand (RANKL)– and macrophage colony‐stimulating factor (M‐CSF)–stimulated in vitro osteoclastogenesis and bone resorption in TN/CD115⁺ cells. In the periphery, 14 days of treatment increased the percentage and absolute numbers of HSCs (Lin^?CD117⁺Sca‐1⁺) in the spleen (p < .05). These data correlated with an increase in the percent and absolute numbers of HSCs in bone marrow on day 14 (p < .05). Interestingly, the effects on hematopoietic progenitors do not depend on osteoclast resorption activity. These results suggest that in vivo PTH treatment increased in vitro osteoclastogenesis and resorption without altering the number of osteoclast precursors. This implies that in vivo PTH induces sustained changes, possibly through an epigenetic mechanism, in the in vitro responsiveness of the cells to M‐CSF and RANKL. © 2011 American Society for Bone and Mineral Research.     

Therapeutic Efficacy of Combined Intraoperative Ablation and Resection for Colorectal Liver Metastases: An International,Multi-institutional Analysis

Background  

Only 10–25% of patients presenting with colorectal liver metastases (CRLM) are amenable to hepatic resection. By combining resection and ablation, the number of patients eligible for surgery can be expanded. We sought to determine the efficacy of combined resection and ablation for CRLM.