EN BLOC NEPHRECTOMY IN PATIENTS UNDERGOING POST-CHEMOTHERAPY RETROPERITONEAL LYMPH NODE DISSECTION FOR NONSEMINOMATOUS TESTIS CANCER: INDICATIONS, IMPLICATIONS AND OUTCOMES

Purpose

We review the indications for nephrectomy at post-chemotherapy retroperitoneal lymph node dissection, identify patients at risk for nephrectomy and assess the impact of nephrectomy on outcome.

Materials and Methods

Using a computerized data base and chart review we retrospectively reviewed the records of 848 patients who underwent retroperitoneal lymph node dissection after chemotherapy.

Results

En bloc nephrectomy was performed at retroperitoneal lymph node dissection after chemotherapy in 162 of the 848 patients (19%). The indications for nephrectomy included contiguous involvement of perirenal structures in 73% of the cases, renal vein thrombosis in 6%, a poorly functioning or nonfunctioning renal unit in 5% and a combination of these conditions in 16%. Pathological studies of the hilum revealed cancer in 20% of the cases, teratoma in 49% and fibrosis in 31%. Patients requiring nephrectomy had significantly more advanced disease and larger disease volume at presentation and after chemotherapy. There were no significant differences in perioperative morbidity or mortality compared with patients who did not undergo nephrectomy. Only 3 patients required perioperative dialysis and none required long-term renal support.

Conclusions

These findings support en bloc nephrectomy at post-chemotherapy retroperitoneal lymph node dissection in select patients with large volume perihilar retroperitoneal disease.     

Morphometric studies of secretory granule formation in mouse pancreatic acinar cells. Dissecting the early structural changes following pilocarpine injection

Secretory granule formation in pancreatic acinar cells is known to involve massive membrane flow. In previous studies we have undertaken morphometry of the regranulation mechanism in these cells and in mast cells as a model for cellular membrane movement. In our current work, electron micrographs of pancreatic acinar cells from ICR mice were taken at several time points after extensive degranulation induced by pilocarpine injection in order to investigate the volume changes of rough endoplasmic reticulum (RER), nucleus, mitochondria and autophagosomes. At 2–4 h after stimulation, when the pancreatic cells demonstrated a complete loss of granules, this was accompanied by an increased proportion of autophagosomal activity. This change primarily reflected a greatly increased proportion of profiles retaining autophagic vacuoles containing recognisable cytoplasmic structures such as mitochondria, granule profiles and fragments of RER. The mitochondrial structures reached a significant maximal size 4 h following injection (before degranulation 0.178±0.028 μm³; at 4 h peak value, 0.535±0.109 μm³). Nucleus size showed an early volume increase approaching a maximum value 2 h following degranulation. The regranulation span was thus divided into 3 stages. The first was the membrane remodelling stage (0–2 h). During this period the volume of the RER and secretory granules was greatly decreased. At the intermediate stage (2–4 h) a significant increase of the synthesis zone was observed within the nucleus. The volume of the mitochondria was increasing. At the last step, the major finding was a significant granule accumulation in parallel with an active Golgi zone.     

Efficacy of Medical Therapy for the Reduction of Heart Failure Events in Patients with Implanted Cardioverter Defibrillators

Background : Prophylactic therapy with the implantable cardioverter defibrillator (ICD) reduces the mortality among patients with left ventricular dysfunction; however, life-prolonging device therapy has been shown to be associated with an increased risk for subsequent heart failure (HF) events. There are limited data on the effect of the primary types of HF medications, angiotensin converting enzyme inhibitors (ACE-I), and beta-blockers on HF progression in ICD-treated patients.
Methods : Multivariate Cox proportional hazards regression analysis was used to assess the effect of time-dependent medical therapy with ACE-I and beta-blockers on the development of HF in patients with an ICD in the Multicenter Automatic Defibrillator Trail (MADIT) II.
Results: In multivariate analysis, ICD therapy was associated with a significant 39% increase in the risk of HF as compared with conventional medical therapy. ACE-I and beta-blockers exhibited a graded efficacy for the reduction in the risk of HF events in ICD-treated patients: the greatest risk reduction of HF was seen in patients taking combination therapy (HR = 0.36, P < 0.001), followed by patients using beta-blockers only (HR = 0.51, P = 0.017) and ACE-I only (HR = 0.64, P = 0.071). Beta-blocker subtypes (metoprolol [HR = 0.49, P = 0.001] and carvedilol [HR = 0.58, P = 0.004]) exhibited similar efficacy. Consistent results were demonstrated when the combined endpoint of HF or death was assessed.
Conclusions : ICD-treated patients experience an increased risk for HF events that can be significantly attenuated by medical therapy with beta-blockers and ACE-inhibitors.     

Gastrointestinal involvement in homocystinuria

Abstract Homocystinuria is frequently associated with severe multisystem involvement such as dislocated lenses, skeletal deformities, mental retardation and premature vascular occlusions. Surprisingly, gastro-intestinal involvement has not been described in this disorder. We present a 17 year old boy with homocystinuria due to cystathionine beta-synthase deficiency, who developed severe gastrointestinal involvement, manifested by chronic diarrhoea and acute pancreatitis. The diarrhoea was successfully treated with betaine. Possible pathophysiological mechanisms and suggested treatment are described.     

On the Etiology of "Meat Anemia" in Mice

Young mice kept on a diet consisting of meat only develop an anemiawhich is accompanied by depressed growth and high fatality.

Treatment of mice while subsisting on the meat diet with para-aminobenzoic acid, folic acid, vitamin B₁₂, liver extract, pyridoxine, iron, vitaminA, penicillin, aureomycin or a combination of some of these substancesneither prevents the anemia nor the mortality, nor does it improve growth.Some of these substances have, however, a slight effect in preventing anemia.

Replacing one of four parts of meat by beef liver or an isocaloric-isonitrogenous mixture of casein, cornstarch, salts and water almost completely prevents the anemia but does not improve, or only slightly improves, the stuntedgrowth. Dilution of meat with liver but not with the casein mixture has astriking therapeutic effect in mice rendered anemic by the meat diet.

It is assumed that the anemia is caused by the presence in meat of a hematopoiesis-inhibiting factor and/or by the lack of some unknown hematopoieticfactor(s) possibly produced by the intestinal flora and present in liver.

Submitted on September 8, 1959 Accepted on January 4, 1960     

Permanent Pacemaker Implantation Following Cardiac Surgery: Indications and Long-Term Follow-Up

Background: Conduction disturbances requiring permanent pacemaker implantation after heart surgery occur in about 1.5% of patients. Early pacemaker implantation may reduce morbidity and postoperative hospital stay. We reviewed our experience with patients undergoing surgery to try and identify predictors for pacemaker requirements and patients who will remain pacemaker dependent.
Methods: We performed a retrospective review of 4,999 patients undergoing surgery between the years 1993 and 2005. Patient age was 64 ± 12 years, and 71% were males. Coronary bypass was performed in 4,071 (81%), aortic valve replacement in 675 (14%), and mitral valve replacement in 968 (18%) patients.
Results: Seventy-two patients (1.4%) required implantation of a permanent pacemaker after surgery. Indications for pacemaker implantation included complete atrioventricular block in 59, symptomatic bradycardia/slow atrial fibrillation in nine, second-degree atrioventricular block in two, and other conduction disturbances in two patients. Predictors for pacemaker requirement by multivariate analysis were left bundle branch block and aortic valve replacement (P < 0.001). Late follow-up was available in 58 patients, at 72 ± 32 months. Thirty-seven (63%) were pacemaker dependent. Predictors for late pacemaker dependency were third-degree atrioventricular block after surgery and preoperative left bundle branch block (P < 0.001).
Conclusions: Patients at high risk for pacemaker implantation after heart surgery include those with preexisting conduction disturbances, and those undergoing aortic valve replacement. Of those receiving a pacemaker, about one-third will recover at late follow-up. For patients in the high-risk group who are pacemaker dependent after surgery, we recommend implanting a permanent pacemaker at 5 days after surgery, thus enabling early mobilization and early discharge.