Focal laser ablation as clinical treatment of prostate cancer: report from a Delphi consensus project.

PURPOSE: To define the role of focal laser ablation (FLA) as clinical treatment of prostate cancer (PCa) using the Delphi consensus method. METHODS: A panel of international experts in the field of focal therapy (FT) in PCa conducted a collaborative consensus project using the Delphi method. Experts were invited to online questionnaires focusing on patient selection and treatment of PCa with FLA during four subsequent rounds. After each round, outcomes were displayed, and questionnaires were modified based on the comments provided by panelists. Results were finalized and discussed during face-to-face meetings. RESULTS: Thirty-seven experts agreed to participate, and consensus was achieved on 39/43 topics. Clinically significant PCa (csPCa) was defined as any volume Grade Group 2 [Gleason score (GS) 3+4]. Focal therapy was specified as treatment of all csPCa and can be considered primary treatment as an alternative to radical treatment in carefully selected patients. In patients with intermediate-risk PCa (GS 3+4) as well as patients with MRI-visible and biopsy-confirmed local recurrence, FLA is optimal for targeted ablation of a specific magnetic resonance imaging (MRI)-visible focus. However, FLA should not be applied to candidates for active surveillance and close follow-up is required. Suitability for FLA is based on tumor volume, location to vital structures, GS, MRI-visibility, and biopsy confirmation. CONCLUSION: Focal laser ablation is a promising technique for treatment of clinically localized PCa and should ideally be performed within approved clinical trials. So far, only few studies have reported on FLA and further validation with longer follow-up is mandatory before widespread clinical implementation is justified.

Peroxisome proliferator-activated receptor δ promotes the progression of posttraumatic osteoarthritis in a mouse model.

OBJECTIVE: Osteoarthritis (OA) is a serious disease of the entire joint, characterized by articular cartilage degeneration, subchondral bone changes, osteophyte formation, and synovial hyperplasia. Currently, there are no pharmaceutical treatments that can slow the disease progression, resulting in greatly reduced quality of life for patients and the need for joint replacement surgeries in many cases. The lack of available treatments for OA is partly due to our incomplete understanding of the molecular mechanisms that promote disease initiation and progression. The purpose of the present study was to examine the role of the nuclear receptor peroxisome proliferator-activated receptor δ (PPARδ) as a promoter of cartilage degeneration in a mouse model of posttraumatic OA. METHODS: Mouse chondrocytes and knee explants were treated with a pharmacologic agonist of PPARδ (GW501516) to evaluate changes in gene expression, histologic features, and matrix glycosaminoglycan breakdown. In vivo, PPARδ was specifically deleted from the cartilage of mice. Histopathologic scoring according to the Osteoarthritis Research Society International (OARSI) system and immunohistochemical analysis were used to compare mutant and control mice subjected to surgical destabilization of the medial meniscus (DMM). RESULTS: In vitro, PPARδ activation by GW501516 resulted in increased expression of several proteases in chondrocytes, as well as aggrecan degradation and glycosaminoglycan release in knee joint explants. In vivo, cartilage-specific PPARδ-knockout mice did not display any abnormalities of skeletal development but showed marked protection in the DMM model of posttraumatic OA (as compared to control littermates). OARSI scoring and immunohistochemical analyses confirmed strong protection of mutant mice from DMM-induced cartilage degeneration. CONCLUSION: These data demonstrate a catabolic role of endogenous PPARδ in posttraumatic OA and suggest that pharmacologic inhibition of PPARδ is a promising therapeutic strategy.

Percutaneous tamponade of inadvertent transthoracic catheterization of the aorta.

During routine placement of a subclavian central venous catheter for cancer chemotherapy, a sheath was inadvertently placed into the aortic arch, through the left lung. We describe a technique for transthoracic compression of the aortic injury using the sheath in conjunction with an occlusion balloon catheter.

Regional disposal of intravenously infused glucose during prolonged hyperglycemia-hyperinsulinemia.

We measured splanchnic and leg glucose uptake during prolonged (i.e., 15 hours), moderate hyperglycemia-hyperinsulinemia (clamp). Plasma free fatty acid (FFA) concentration was maintained at basal concentration during the clamp via infusion of exogenous lipids and heparin in healthy volunteers to create a metabolic profile similar to glucose intolerance (i.e., hyperglycemia-hyperinsulinemia with elevated FFA concentration). During the clamp, glucose was infused at an average rate of 49 +/- 4 micromol/kg/min, which resulted in a plasma glucose concentration of 8.8 +/- 0.5 mmol/L compared with a concentration of 4.4 +/- 0.2 mmol/L in the basal state (P < 0.05). Insulin concentration increased from 5.5 +/- 1.1 microU/mL (basal) to 31.3 +/- 12.7 microU/mL (clamp; P < 0.05), whereas plasma FFA concentration was similar in the two conditions (3.9 +/- 0.5 mmol/L and 4.1 +/- 0.5 mmol/L, basal and clamp, respectively). Glucose balance across the splanchnic region switched from net release (-5.8 +/- 0.7 micromol/kg/min) in the basal state to net uptake in the clamp (19.8 +/- 3.7 micromol/kg/min; P < 0.05) and accounted for approximately 40% of the infused glucose. Glucose uptake across the leg was 0.7 +/- 0.2 micromol/kg/min (basal) and 5.5 +/- 2.2 micromol/kg/min (clamp; P < 0.05). In summary, tissues in the splanchnic region (i.e., liver) are important for disposal of intravenously infused glucose during prolonged, moderate hyperglycemia-hyperinsulinemia. Accelerated hepatic glucose uptake may disrupt normal liver metabolism, with potentially dangerous consequences for the patient. Measures to control systemic glucose concentration may be necessary to prevent excessive glucose disposal in the liver.

Tc-99m sestamibi imaging of a pancreatic VIPoma and parathyroid adenoma in a patient with multiple type I endocrine neoplasia.

Technetium-99m sestamibi is known to localize in primary malignant and metastatic tumors. Specifically, brain, breast, thyroid, parathyroid, lung, and kidney tumors have been imaged. The Verner Morrison syndrome, which is caused by excessive vasoactive intestinal peptide (VIP), consists of watery diarrhea, hypokalemia, and achlorhydria. This condition is rarely associated with multiple endocrine neoplasia. The authors present a case of multiple endocrine neoplasia type I with visualization of a pancreatic VIPoma and parathyroid adenoma with Tc-99m MIBI.

Preoperative chemoembolization in patients with hepatocellular carcinoma undergoing liver transplantation: influence of emergent versus elective procedures on patient survival and tumor recurrence rate.

Our purpose was to compare the recurrence rate and survival in patients with hepatocellular carcinoma (HCC) who had elective transarterial chemoembolization (TACE), immediate preoperative TACE, or no treatment prior to orthotopic liver transplantation (OLT). A total of 132 patients with HCC had TACE prior to OLT. Eighteen patients had no TACE before OLT and functioned as a control group. The urgent group included 35 patients embolized less than 24 h before OLT and the elective group included 97 patients embolized greater than 1 day before transplantation. These groups were compared with regard to tumor staging, hepatic synthetic function, and post-TACE tumor necrosis and survival and recurrence rates. Patients were followed for a mean of 780 days post OLT (1-2912 days). The tumor staging was similar between groups but the Childs-Pugh score in the urgent and untreated group was significantly higher than that of the other groups. The degree of necrosis at explant was also significantly different between the two treated groups, with an average 35% necrosis in the patients embolized less than 24 h before OLT vs 77% in the elective group (p < 0.002). Recurrence rate in the urgent group was 8 of 35 (23%) in a median of 580 days, 20 of 97 (21%) in a median of 539 days in the elective group, and 2 of 18 (11%) in a median of 331 days in the no-TACE group. Survival at 1, 3, and 5 years was 91%, 80%, and 72% in the elective group, 79%, 58%, and 39% in the urgent group, and 69%, 61%, and 41% in the no-TACE group, respectively. The urgent and no-TACE groups had significantly worse survival compared with the other groups; however, the tumor recurrence rates were statistically the same among all three groups. TACE within 24 h of OLT causes an average of 35% necrosis and elective TACE increases necrosis further to 77%. Despite this difference, the tumor recurrence rate in the three groups is equivalent and no different from that in the group that received no treatment before OLT. The decreased survival in the immediate and no-TACE groups was due to non-cancer-related deaths.

[An attack of glaucoma after a cataract operation associated with pigment degeneration of the retina (author's transl)]. / Glaukomanfall nach Kataraktoperation bei Pigment-degeneration der Netzhaut

From four cases the appearance of acute glaucoma attacks after cataract-operation in association with pigment degeneration of the retina is described. We could show in none of the cases the previous presence of glaucoma. It is concluded from this there is an increased danger of an acute pressure rise in operative procedures in association with pigment degeneration of the cornea as a result of dysregulation of the intraocular fluid mechanics. Appropriate preventive measures are recommended.

[Possibilities and limitations in orbital surgery from an ophthalmological point of view]. / Uber Möglichkeiten und Grenzen der Orbitachirurgie aus ophthalmologischer Sicht.

Since it is possible to approach orbit either from outside or through the cranial cavity, orbital surgery constitutes a borderline field between ophthalmic surgery, facial and neurosurgery. With reference to characteristic cases of space-occupying orbital tumors, an attempt is made to point out limitations and surgical possibilities from the ophthalmological point of view. In this connection, Krönlein's operation, which has almost been forgotten, is described and illustrated with original pictures.

Some aspects of maternal behaviour in mammals.

Lactation is the one common factor in the behaviour patterns of maternal care in mammals. A series of behaviour patterns is elicited by the different stages of the developing young and these are related to the way of life of the animals concerned. Infants which are born naked, blind and helpless elicit retrieving and nest building and are cleaned and cared for by the female. Older animals or those born with fur, but with poor locomotion, are still carried and cleaned. When the young can move well other behaviour patterns which keep the young and mother together are important, so signals for communication and recognition of individuals develop. At the end of lactation various behaviour patterns bring about weaning. Sometimes this is the result of dispersal by the young, and sometimes the young are actively rejected or deliberately abandoned. Several examples of maternal behaviour are given in relation to the classes of mammals and some related problems are discussed.

[The disease picture of severe blepharospasm, the cause and a new kind of treatment with long-term results]. / Das Krankheitsbild des Blepharospasmus gravis, Ursache und neuartige Behandlung mit Langzeitergebnissen.

The etiology of essential blepharospasm is extraordinarily manifold and still not clarified in many instances. The therapeutic possibilities are equally manifold and not always satisfactory. A new method of surgical intervention consists in the dissection of the zygomaticotemporal nerve shortly after its separation from the stem of the facial nerve. In 10 cases with particularly severe blepharospasm, a permanent therapeutic result which was satisfactory in every respect was achieved in collaboration with an otorhinolaryngologist. For the ophthalmologist and otorhinolaryngologist a knowledge of the various therapeutic possibilities is important in order to adjust treatment accordingly.

Mutual recognition between ewes and lambs.

Studies to investigate the relative value of sight, hearing and smell in mutual recognition between ewes and lambs are described. The method used was to alter clues that could aid in recognition, rather than interfering with the animal's sensory perception. When lambs were coloured with powdered dyes to change appearance, this produced marked avoidance by the dams of the treated lambs. When lambs were partially coloured, the ewes' greatest reaction was shown to lambs whose heads were coloured. Other experiments compared the role of vision and hearing by observing recognition when the ewes or lambs were hidden behind screening, or muted. The results indicate that while olfaction is important for recognition when the ewe and lamb are close together, visual clues are of major importance in maternal discrimination and auditory clues are important for the lambs as they get older.

Diffuse ileal conduit stenosis from Crohn's disease.

A case of Crohn's disease affecting an ileal loop urinary conduit presented as a diffuse loop stenosis and bilateral hydronephrosis. Radiologic appearance and histology are analyzed to differentiate this unusual complication from other causes of conduit stricture.

Hepatic perfusion before and after the transjugular intrahepatic portosystemic shunt procedure: impact on survival.

PURPOSE: This study correlates transjugular intrahepatic portosystemic shunt (TIPS) mortality with flow patterns in the cirrhotic liver. MATERIALS AND METHODS: Twenty-seven TIPS patients and 10 control subjects were used for this study. The authors evaluated hepatic perfusion with venous injections of Tc-99m pertechnetate before and after TIPS. Hepatic time-activity curves were analyzed for type and amount of liver perfusion. These parameters were correlated with survival for a mean follow-up of 18 months. RESULTS: The mean arterial contribution to liver blood flow was 25.4% in the normal control patients, 39.9% in patients prior to TIPS, and increased to 48.3% after TIPS. Although the proportion of arterial supply to the cirrhotic liver varied widely, TIPS mortality did not correlate with the preprocedure hepatic artery/portal venous perfusion ratio. However, patients with both an "arterialized" flow pattern and low total hepatic perfusion had higher mortality, with a mean survival of 2 months compared to patients with a more favorable perfusion profile (mean survival, 28.4 months). CONCLUSIONS: The proportion of arterial perfusion to the liver before TIPS did not affect survival. However, patients with a combination of reduced total hepatic perfusion and an arterial flow pattern had poorer survival, suggesting that both the quantity and quality of hepatic perfusion predicts TIPS outcome.

Interventional radiology of the biliary tract.

Interventional radiology provides a range of management options applicable to a broad spectrum of patients with biliary tract disorders. This review highlights the importance of these procedures, and illustrates their safety and effectiveness. Percutaneous transcatheter decompression has a well-established role in the management of patients with benign and malignant biliary obstruction. The advent of metallic stents has greatly increased the value of these techniques. Patients with biliary tract calculi can be successfully treated with a variety of percutaneous techniques, obviating surgery and providing a useful alternative to endoscopic methods. Finally, percutaneous cholecystostomy has evolved as a valuable adjunct in the treatment of calculous cholecystitis, as well as providing the definitive cure for many patients with acalculous cholecystitis.

Hyperglycemia-induced inhibition of splanchnic fatty acid oxidation increases hepatic triacylglycerol secretion.

The effect of hyperglycemia ( approximately 8 mmol/l) on splanchnic fatty acid oxidation and triacylglycerol (TG) secretion rates was investigated in five healthy men. U-13C-labeled fatty acids were infused to estimate fatty acid kinetics and oxidation across the splanchnic region, and in vivo labeled very low density lipoprotein (VLDL)-TG was infused to estimate TG secretion rate. Plasma fatty acid carbon enrichment and concentration were maintained constant by infusion of lipids and heparin in the hyperglycemia experiments. Fatty acid uptake by the splanchnic region was 1.4 +/- 0.2 and 2.2 +/- 0.9 micromol. kg-1. min-1 in the basal and clamp experiments, respectively, whereas fatty acid oxidation decreased from 0.4 +/- 0. 04 to 0.2 +/- 0.05 micromol. kg-1. min-1 (P < 0.05). Hepatic TG secretion increased from 0.35 +/- 0.07 micromol. kg-1. min-1 in the basal state to 0.53 +/- 0.11 micromol. kg-1. min-1 after 15 h of hyperglycemia (P < 0.05). Similarly, plasma VLDL-TG concentration increased from 0.28 +/- 0.06 to 0.43 +/- 0.05 mmol/l during the clamp (P < 0.05). In summary, hyperglycemia attenuates fatty acid oxidation in the splanchnic region in human volunteers, even when fatty acid availability is constant. This adaptation results in a significant increase in the VLDL-TG secretion rate and concentration in plasma.

Effect of hyperglycemia-hyperinsulinemia on whole body and regional fatty acid metabolism.

The effects of combined hyperglycemia-hyperinsulinemia on whole body, splanchnic, and leg fatty acid metabolism were determined in five volunteers. Catheters were placed in a femoral artery and vein and a hepatic vein. U-13C-labeled fatty acids were infused, once in the basal state and, on a different occasion, during infusion of dextrose (clamp; arterial glucose 8.8 +/- 0.5 mmol/l). Lipids and heparin were infused together with the dextrose to maintain plasma fatty acid concentrations at basal levels. Fatty acid availability in plasma and fatty acid uptake across the splanchnic region and the leg were similar during the basal and clamp experiments. Dextrose infusion decreased fatty acid oxidation by 51.8% (whole body), 47.4% (splanchnic), and 64.3% (leg). Similarly, the percent fatty acid uptake oxidized decreased at the whole body level (53 to 29%), across the splanchnic region (30 to 13%), and in the leg (48 to 22%) during the clamp. We conclude that, in healthy men, combined hyperglycemia-hyperinsulinemia inhibits fatty acid oxidation to a similar extent at the whole body level, across the leg, and across the splanchnic region, even when fatty acid availability is constant.

Regional acetate kinetics and oxidation in human volunteers.

We have used a 3-h primed continuous infusion of [1,2-13C]acetate in five fasted (24 h) volunteers to quantify splanchnic and leg acetate metabolism (protocol 1). Fractional extraction of acetate by both tissues was high ( approximately 70%), and simultaneous uptake and release of acetate were observed. Labeled carbon recovery in CO2 was 37.9 +/- 2.3% at the whole body level, 37.7 +/- 1.5% across the splanchnic bed, and 37.3 +/- 2.9% across the leg. Furthermore, we calculated whole body labeled carbon recovery during 15 h of [1, 2-13C]acetate infusion in three volunteers (protocol 2). Whole body acetate carbon recovery in CO2 was significantly higher (66.7 +/- 4. 5%) after 15 h of tracer infusion than after 3 h. We conclude that acetate is rapidly taken up by the leg and splanchnic tissues and that the percent recovery of CO2 from the oxidation of acetate is heavily dependent on the length of acetate tracer infusion. In the postabsorptive state, labeled carbon recovery from acetate across the leg and the splanchnic region is similar to the whole body CO2 recovery.