Combined androgen blockade in the management of advanced prostate cancer: A sensible or ostensible approach

BACKGROUND: To compare the efficacy of orchiectomy alone and orchiectomy plus flutamide in treating patients with advanced carcinoma prostate. MATERIALS AND METHODS: The study was initiated on 1 July 1997 and closed after enrolling 100 patients on 30 June 2000. Patients were prospectively randomized to orchiectomy alone (O) and orchiectomy plus flutamide (OF). A complete response (CR) was defined as the normalization of bone scans and serum prostate-specific antigen (PSA) levels returning to normal (< 4 ng/mL). A partial response (PR) was defined as a 50% reduction in metastasis mass compared to the initial study or a decrease in the PSA level of 50% of the initial value. Progressive disease (PD) was defined as the development of any new hot spot on bone scan or any increase in previously existing PSA level by 25%. RESULTS: A total of 100 patients were entered in the study. The maximum percentage change in PSA levels in both groups was found in the first 3 months after orchiectomy, that is, 95% and 97% for the O and OF groups, respectively. In more than 80% of the patients this decrease in PSA was maintained for 3 years. The mean percentage change at 3 years in the O and OF groups was 70% and 75% (P = 0.95), respectively, and the overall response rate (CR + PR) was 88.50% and 86.53% in the two groups, respectively (P = 0.85). The follow-up period ranged between 3 and 5 years (mean, 3.5 years). The mean time to progression was 27 and 29 months in the O and OF groups, respectively. The overall survival rate at 3 and 5 years in two treatment groups was 45.83% and 48.07%, 20.83% and 23.07% in the O and OF groups, respectively (P = 0.75). CONCLUSIONS: Maximum percentage decrease in PSA is seen within the first 3 months of therapy. Orchiectomy alone is as effective as combination therapy in decreasing serum PSA. Overall survival at 3 and 5 years in the orchiectomy only group was as good as that of combination therapy. These data suggest that the routine addition of flutamide to orchiectomy is not advisable.     

Integration of Merged Delayed‐Enhanced Magnetic Resonance Imaging and Multidetector Computed Tomography for the Guidance of Ventricular Tachycardia Ablation: A Pilot Study

MDCT/MRI Fusion for the Guidance of VT Ablation . Background: Delayed enhancement (DE) MRI can assess the fibrotic substrate of scar‐related VT. MDCT has the advantage of inframillimetric spatial resolution and better 3D reconstructions. We sought to evaluate the feasibility and usefulness of integrating merged MDCT/MRI data in 3D‐mapping systems for structure–function assessment and multimodal guidance of VT mapping and ablation. Methods: Nine patients, including 3 ischemic cardiomyopathy (ICM), 3 nonischemic cardiomyopathy (NICM), 2 myocarditis, and 1 redo procedure for idiopathic VT, underwent MRI and MDCT before VT ablation. Merged MRI/MDCT data were integrated in 3D‐mapping systems and registered to high‐density endocardial and epicardial maps. Low‐voltage areas (<1.5 mV) and local abnormal ventricular activities (LAVA) during sinus rhythm were correlated to DE at MRI, and wall‐thinning (WT) at MDCT. Results: Endocardium and epicardium were mapped with 391 ± 388 and 1098 ± 734 points per map, respectively. Registration of MDCT allowed visualization of coronary arteries during epicardial mapping/ablation. In the idiopathic patient, integration of MRI data identified previously ablated regions. In ICM patients, both DE at MRI and WT at MDCT matched areas of low voltage (overlap 94 ± 6% and 79 ± 5%, respectively). In NICM patients, wall‐thinning areas matched areas of low voltage (overlap 63 ± 21%). In patients with myocarditis, subepicardial DE matched areas of epicardial low voltage (overlap 92 ± 12%). A total number of 266 LAVA sites were found in 7/9 patients. All LAVA sites were associated to structural substrate at imaging (90% inside, 100% within 18 mm). Conclusion: The integration of merged MDCT and DEMRI data is feasible and allows combining substrate assessment with high‐spatial resolution to better define structure–function relationship in scar‐related VT. (J Cardiovasc Electrophysiol, Vol. 24, pp. 419‐426, April 2013)     

Protein Losing Enteropathy as a Manifestation of Henoch-Schönlein Purpura

ABSTRACT. Gastrointestinal manifestations of Henoch-Schönlein purpura (HSP) commonly include abdominal pain and gastrointestinal bleeding. Hypoproteinemia and edema could be related to renal involvement. We report a 14-year-old boy with classical features of HSP manifestated with edema due to severe intestinal protein loss, measured by elevated fecal alpha 1 antitrypsin secretion. The protein losing enteropathy subsided with corticosteroid therapy.     

Complications of laparoscopic radical cystectomy during the initial experience

AIM: Radical cystectomy is the standard of care for patients with muscle invasive bladder cancer. While open radical cystectomy is now a standard procedure, laparoscopic radical cystectomy is still in its infancy. We performed this surgery laparoscopically in 11 patients and review the procedure specific complications. METHODS: Beginning in February 1999, 11 patients underwent laparoscopic radical cystectomy at the Department of Urology, All India Institute of Medical Sciences, New Dehli. Urinary diversion was performed by an open-hand sewn ileal conduit. RESULTS: There were three intraoperative complications specifically related to the laparoscopic radical cystectomy. These included injury to the external iliac vein in one patient and a small rectal tear in two. All were repaired with laparoscopic free hand suturing with normal postoperative recovery. Other laparoscopy-related complications were subcutaneous emphysema in one patient and hypercarbia necessitating conversion to open surgery in a patient who, four weeks after surgery, died of multiple organ failure. One patient had margins positive and received cisplatinum-based chemotherapy. All patients had normal renal function and preserved upper tracts with no evidence of metastasis at a mean of 18.4 months follow up (range 1-48 months). CONCLUSIONS: Though there were three complications specific to the laparoscopic radical cystectomy, none necessitated a conversion to open surgery or hampered the overall outcome. Absence of local recurrence or metastatic disease at four years of follow up suggests that the procedure is oncologically valid. Laparoscopic radical cystectomy is a new procedure and it is important to critically analyze the complications in order to reduce their occurrence and allow the development of a better technique.     

Mitral Isthmus Block in a Case of Persistent Left Superior Vena Cava

Mitral Isthmus Block in Superior Vena Cava . Persistent left superior vena cava (LSVC), an uncommon venous anomaly, could be an arrhythmogenic source of atrial fibrillation. Multiple electrical connections were reported between the LSVC and the left atrium, which may negatively impact the achievement of conduction block during linear ablation of left mitral isthmus. We describe a case with perimitral atrial flutter (AFL) in a patient with isolated LSVC. AFL was successfully treated and complete perimitral conduction block was achieved following a lengthy epicardial radiofrequency application. (J Cardiovasc Electrophysiol, Vol. 22, pp. 343‐345, March 2011)     

A 90-Day Subcutaneous Toxicity and Fertility Study of a LHRH Antagonist in Rats

A 90-Day Subcutaneous Toxicity and Fertility Study of a LHRHAntagonist in Rats. SUNDARAM, K., DIDOLKAR, A. K., KEIZER-ZUCKER,A., DEJESUS, W., RIVIER, J., VALE, W., AND BARDIN, C. W. (1990).Fundam. Appl. Toxicol. 14, 734–744. [Ac-D2Nal¹,4Cl-DPhe²,D3Pal³,Arg⁵,DGlu⁶(anisole adduct),DAla¹⁰]-GnRH (Nal-Glu) is an antagonist ofLHRH and has the potential to be utilized as an antigonadalagent. A study was undertaken to evaluate the toxicologicaleffects of Nal-Glu in rats. Nal-Glu, dissolved in 5% mannitolin water containing 9 ml/liter benzyl alcohol, was administeredsubcutaneously. In subchronic studies, groups of 12 male and12 female rats received 0, 50, 250, or 1250 µg/kg bodyweight (BW) Nal-Glu for 90 days and were killed on Day 91. Additionalgroups of male and female rats were given the high dose of Nal-Glu(1250 µ/kg BW) or vehicle for either 30 or 90 days. Theirfertility was assessed by mating them with normal animals. Unlikesome other LHRH antagonists, Nal-Glu exhibited a low potencyfor causing in vitro histamine release from rat peritoneal mastcells. Furthermore, in acute In vivo studies, Nal-Glu was lessactive in the induction of peripheral edema. In the subchronicstudy, all doses of Nal-Glu were well tolerated and there wereno apparent systemic toxic effects. The pharmacological effectsof Nal-Glu were quite evident, however. Nal-Glu treatment ledto a significantly decreased body weight gain in the males anda significantly increased body weight gain in the females. Therewas a dose-dependent decrease in weights of gonads and reproductiveorgans in both the sexes. Some of the hematological and serologicalparameters were significantly different in Nal-Glu-treated animals.However, most of the values were within the normal range andare considered to be of no toxicological significance. Histopathologicalevaluations were made in the control and high-dose groups only.In the male, a seminiferous tubular degeneration and atrophyof the interstitial cells was seen. The prostate and seminalvesicles were also atrophied and the epididymides were devoidof spermatozoa. In the females, the ovaries and uteri were atrophic.The injection site of Nal-Glu-treated rats had inflammatorychanges indicative of a local irritating action of the drug.All other tissues had normal histomorphology. Both male andfemale rats became infertile when 1250 MgAg Nal-Glu was administeredfor 30 days. Normal fertility was restored 8 weeks after cessationof 90-day treatment. It is concluded that repeated administrationof Nal-Glu leads to reversible infertility in both male andfemale rats. Although it was irritating at the site of injection,Nal-Glu had no systemic toxicological effects.