IGF-I treatment in adults with type 1 diabetes: effects on glucose and protein metabolism in the fasting state and during a hyperinsulinemic-euglycemic amino acid clamp

Type 1 diabetes is associated with abnormalities of the growth hormone (GH)-IGF-I axis. Such abnormalities include decreased circulating levels of IGF-I. We studied the effects of IGF-I therapy (40 microg x kg(-1) x day(-1)) on protein and glucose metabolism in adults with type 1 diabetes in a randomized placebo-controlled trial. A total of 12 subjects participated, and each subject was studied at baseline and after 7 days of treatment, both in the fasting state and during a hyperinsulinemic-euglycemic amino acid clamp. Protein and glucose metabolism were assessed using infusions of [1-13C]leucine and [6-6-2H2]glucose. IGF-I administration resulted in a 51% rise in circulating IGF-I levels (P < 0.005) and a 56% decrease in the mean overnight GH concentration (P < 0.05). After IGF-I treatment, a decrease in the overnight insulin requirement (0.26+/-0.07 vs. 0.17+/-0.06 U/kg, P < 0.05) and an increase in the glucose infusion requirement were observed during the hyperinsulinemic clamp (approximately 67%, P < 0.05). Basal glucose kinetics were unchanged, but an increase in insulin-stimulated peripheral glucose disposal was observed after IGF-I therapy (37+/-6 vs. 52+/-10 micromol x kg(-1) x min(-1), P < 0.05). IGF-I administration increased the basal metabolic clearance rate for leucine (approximately 28%, P < 0.05) and resulted in a net increase in leucine balance, both in the basal state and during the hyperinsulinemic amino acid clamp (-0.17+/-0.03 vs. -0.10+/-0.02, P < 0.01, and 0.25+/-0.08 vs. 0.40+/-0.06, P < 0.05, respectively). No changes in these variables were recorded in the subjects after administration of placebo. These findings demonstrated that IGF-I replacement resulted in significant alterations in glucose and protein metabolism in the basal and insulin-stimulated states. These effects were associated with increased insulin sensitivity, and they underline the major role of IGF-I in protein and glucose metabolism in type 1 diabetes.     

Effect of Pneumoperitoneum on Renal Function and Physiology in Patients Undergoing Robotic Renal Surgery

Laparoscopic and minimally-invasive robotic access has transformed the delivery of urological surgery. While associated with numerous desirable outcomes including shorter post-operative stay and faster return to preoperative function, these techniques have also been associated with increased morbidity such as reduced renal blood flow and post-operative renal dysfunction. The mechanisms leading to these renal effects complex and multifactorial, and have not been fully elucidated. However they are likely to include direct effects from raised intra-abdominal pressure, and indirect effects secondary to carbon dioxide absorption, neuroendocrine factors and tissue damage from oxidative stress. This review summarises these factors, and highlights the need for further work in this area, to direct novel therapies and guide alterations in technique with the aim of reducing renal dysfunction post-laparoscopic and robotic surgery.Key Words: Pneumoperitoneum, Renal blood flow, Renal dysfunction, Neuroendocrine, Oxidative stress     

Paranasal sinus tumors: Peter MacCallum Cancer Institute experience

BACKGROUND: The purpose of this study was to evaluate the local control, pattern of recurrence, overall survival, and prognostic factors of patients with squamous cell carcinoma (SCC), adenocarcinoma, and undifferentiated carcinoma of the paranasal sinuses (PNS) and nasal cavity (NC) presenting to our center for curative treatment over a 10-year period. METHODS: Between 1991 and 2000, 60 patients with SCC (n = 32), adenocarcinoma (n = 25), and undifferentiated carcinoma (n = 3) of the PNS or NC were identified. Forty patients received surgery and postoperative radiotherapy, four surgery alone; 11, radiotherapy alone; three radical radiotherapy after surgical recurrence; one, chemoradiotherapy and surgery; and one, induction chemotherapy followed by radiotherapy. RESULTS: Forty-seven patients (78%) were seen with T3-4 disease; however, most (92%) were node negative on initial assessment. The predominant failure pattern was local disease persistence or recurrence. The estimated 2- and 5-year local control rates were 63% and 49%, respectively. Orbital and neural invasion significantly affected local control. The estimated 2- and 5 year overall survival rates were 57% and 40%, respectively. CONCLUSIONS: Local failure remains the dominant cause for poor outcome in this group of patients. Because of the proximity of critical normal structures, the ability to perform adequate surgery and to deliver effective radiotherapy is limited in many cases. The use of postoperative concurrent chemoradiotherapy warrants further investigation.     

Assessing the Validity of an Abdominal CT Scoring System in the Diagnosis of Encapsulating Peritoneal Sclerosis

Background and objectives: Encapsulating peritoneal sclerosis (EPS) is a severe peritoneal fibrotic reaction in patients on long-term peritoneal dialysis (PD). The early clinical features may be nonspecific. The purpose of the study is to assess the reliability and diagnostic utility of abdominal CT scanning in the diagnosis of EPS.Design, setting, participants, & measurements: Abdominopelvic CT scans of 27 patients diagnosed with EPS on clinical and radiologic grounds in our unit from 1997 to 2006 were retrospectively analyzed. In addition, 35 control CT scans were scored: 15 from hemodialysis patients (HD controls) and 20 from patients on PD (PD controls). Scans were anonymized and scored independently by three radiologists.Results: Inter-rater agreement was moderate to very good (kappa = 0.40 to 0.75) for peritoneal calcification, bowel distribution, bowel wall thickening, and bowel dilation but poorer for loculation of ascites and peritoneal thickening. There was a strongly significant difference between the total CT scan scores at EPS diagnosis and controls (P < 0.00001). Each individual parameter also showed significant differences between EPS and controls (P < 0.006). Bowel tethering and peritoneal calcification were the most specific parameters, and. loculation was the least discriminatory parameter. Interestingly, prediagnostic scans a median of 1.5 yr before EPS diagnosis were normal or near-normal in 9 of 13 EPS patients.Conclusions: CT scanning is a valid and reliable adjunct to the diagnosis of EPS but may not be useful as a screening tool, as the prediagnostic scans did not show abnormalities in many patients who subsequently developed EPS.Peritoneal dialysis (PD) is an important form of renal replacement therapy enabling patients to have a home-based treatment. Encapsulating peritoneal sclerosis (EPS) is a rare but devastating complication in patients on PD, in which the peritoneum becomes progressively thickened and scarred, enclosing the bowel in fibrous tissue. Clinically, the patients present with recurrent small bowel obstruction, blood-stained dialysis effluent or ascites, and/or malnutrition (1,2). The incidence in case series of PD patients is approximately 1% to 3% and increases with length of time on PD, especially more than 5 yr (3–5). The early clinical features of EPS may be nonspecific and are often not recognized until the patient develops complications, such as bowel obstruction. Abdominopelvic CT scan abnormalities in EPS have previously been documented, including peritoneal thickening, peritoneal calcification, loculated fluid collections, tethering of the small bowel, and bowel wall thickening (6–9). Several of these are open to subjective interpretation, which could result in varying reports when scans are reviewed by different radiologists. Furthermore, the clinical utility, diagnostic importance, and longitudinal changes in the various CT abnormalities have not been systematically analyzed.In this study, CT scans of EPS patients diagnosed in our center and CT scans of control PD and hemodialysis (HD) patients were anonymized and scored in random order by three independent radiologists. Two main questions have been addressed. First, which CT scan abnormalities are detectable in patients with EPS, and do these differ in type or degree from PD patients without clinical EPS or patients with end-stage kidney disease not on PD? Second, are radiologists able to identify these changes sufficiently reliably to make CT scanning diagnostically useful? Longitudinal CT data were also available predating and postdating the diagnosis of EPS in several patients, which gives an insight into temporal changes in CT scans in this disease.     

Serum cytokine levels as markers of paralytic ileus following robotic radical prostatectomy at different pneumoperitoneum pressures

Background:To evaluate intraoperative and postoperative cytokines in patients who underwent robotic prostatectomy (RP) at a pressure of 12 or 15 mm Hg, and the risk of postoperative ileus.Materials and methods:We presented the first series evaluating intraoperative and postoperative cytokines in patients undergoing RP at a pressure of 12 or 15 mm Hg by a single surgeon. Changes in cytokine concentrations were shown to correlate with surgical outcomes and pathological states. The study investigated the changes in cytokine concentrations (interferon-γ, tumor necrosis factor-α, interleukin-1β [IL-1β], IL-2, IL-4, IL-6, IL-12, and IL-17) at different pneumoperitoneum pressures and their potential role in the development of postoperative ileus.Results:The data on 10 consecutive patients confirmed that a lower pneumoperitoneum pressure was associated with lower cytokine levels and a lower risk of ileus. There were increased levels of postoperative interferon-γ, tumor necrosis factor-α, IL-12p70, IL-1β, IL-2, IL-4, and IL-17a at 15 mm Hg when compared to 12 mm Hg.Conclusions:The data indicated that lower pressure RP reduced intra-/postoperative cytokine levels confirming our hypothesis. Larger patient numbers are required to further validate this but the implications of this data will benefit not only urological patients but also other speciality patients undergoing minimally invasive surgery.     

Post-Operative Pain Management in Patients Undergoing Robotic Urological Surgery

Robotic urological surgery is being increasingly performed worldwide. The main focus currently is on the operative technique but post operative patient care is an essential part of the process to make this technique safe and successful. We present a review on multiple analgesic techniques available to prevent and treat pain specifically caused after by urological robotic surgery; this article will explain the mechanism of pain pathways involved in laparoscopic procedures and review current evidence pertaining to systemic and regional analgesia methods.Key Words: Robotic surgery, Pain management, Enhanced recovery     

Developing a Robotic Prostatectomy Service and a Robotic Fellowship Programme – Defining the Learning Curve

Introduction

Robotic radical prostatectomy (RRP) is an established treatment for prostate cancer in selected centres with appropriate expertise. We studied our single-centre experience of developing a RRP service and subsequent training of 2 additional surgeons by the initial surgeon and the introduction of United Kingdom''s first nationally accredited robotic fellowship training programme. We assessed the learning curve of the 3 surgeons with regard to peri-operative outcomes and oncological results.

Patients and Methods

Three hundred consecutive patients underwent RRP between November 2008 and August 2012. Patients were divided into 3 equal groups (Group 1, case 1-100; Group 2, case 101-200; and Group 3, case 201-300). Age, ASA score, preoperative co-morbidities and indications for laparoscopic radical prostatectomy were comparable for all 3 patient groups. Peri-operative and oncological outcomes were compared across all 3 groups to assess the impact of the learning curve for laparoscopic radical prostatectomy. All surgical complications were classified using the Clavien-Dindo system.

Results

The mean age was 60.7 years (range 41-74). There was a significant reduction in the mean console time (p < 0.001), operating time (p < 0.001), mean length of hospital stay (p < 0.001) and duration of catheter (p < 0.001) between the 3 groups as the series progressed. The two most important factors predictive of positive surgical margins (PSM) at RRP were the initial prostate specific antigen (PSA) and tumor stage at diagnosis. The overall PSM rate was 26.7%. For T2/T3 tumors the incidence of PSM reduced as the series progressed (Group 1-22%, Group 2-32% and Group 3-26%). The incidence of major complications i.e. grade Clavien-Dindo system score ≤ III was 2% (6/300).

Conclusion

RRP is a safe procedure with low morbidity. As surgeons progress through the learning curve peri-operative parameters and oncological outcomes improve. This learning curve is not affected by the introduction of a fellowship-training programme. Using a carefully structured mentored approach, RRP can be safely introduced as a new procedure without compromising patient outcomes.Key Words: Robotic radical prostatectomy, Prostate cancer, Learning curve, Fellowship training