Is cryosurgical ablation appropriate for treating hepatocellular cancer?

OBJECTIVE: To examine the feasibility and efficacy of cryosurgical ablation as treatment for patients with cirrhosis with unresectable hepatocellular carcinoma. DESIGN: Retrospective case series. SETTING: A tertiary public hospital and a cancer center. PATIENTS: Twelve patients with cirrhosis with hepatocellular carcinoma (stage II, 2; stage III, 1; stage IVA, 7; stage IVB, 2). INTERVENTIONS: Cryosurgical ablation of all identifiable tumors. Nine patients treated with curative intent were included in the survival analysis, and 3 were treated for palliation. Five patients were treated with preoperative intra-arterial chemoembolization. MAIN OUTCOME MEASURES: Perioperative complications and the effects of tumor stage and chemoembolization were examined. Patient survival and disease-free interval were calculated by life-table analysis. RESULTS: No perioperative deaths occurred and 1 patient had 2 postoperative complications: pneumonia and biloma. The mean survival has been 19 months after cryosurgical ablation and 29 months after diagnosis. Three of the 9 patients treated with curative intent died with recurrence at a mean of 17 months after cryosurgical ablation. Four patients are alive with recurrence at a mean of 19 months after cryosurgical ablation and 38 months after diagnosis. Two patients with stage II disease have no evidence of recurrence 10 and 32 months after cryosurgical ablation. CONCLUSIONS: Cryosurgical ablation is feasible and safe for treatment of hepatocellular carcinoma in patients with cirrhosis. The technique is primarily palliative but may provide a possibility of cure in patients with lower-stage disease.     

The effect of cryosurgical ablation of the prostate on erectile function

OBJECTIVE: To investigate the incidence and identify the possible cause of erectile dysfunction after cryoablation of the prostate. PATIENTS AND METHODS: Erectile function was examined prospectively in 15 sexually active men (aged 59-72 years) who underwent cryoablation of the prostate for clinically localized prostate cancer. Erectile function was assessed before and 6 months after treatment; after intracavernosal injection with 10 micrograms of prostaglandin E1 (PGE1), the degree and duration of erection, the size of the cavernosal arteries, the penile arterial blood flow velocity, and the time to achieve peak flow were evaluated using high-resolution ultrasonography and colour pulsed-Doppler spectral analysis. RESULTS: Post-operatively, all patients initially reported an inability to achieve an erection sufficient for vaginal intercourse. At 6 months' follow-up, erectile dysfunction persisted in nine, with minimal or no response to the intracavernosal PGE1 injections, there was a significant decrease in the peak velocity of blood flow within cavernosal arteries and a significant increase in the time to achieve peak arterial flow. CONCLUSION: Although many factors may contribute to erectile dysfunction after cryoablation of the prostate, vascular injury plays a major role.     

Prostate carcinoma: prostate-specific antigen--and then what?

Based on its exclusive organspecificity, prostate specific antigen (PSA) holds a key role in diagnosis and follow up of prostatic carcinoma. for intermediate PSA levels of 4-10 ng/mL, differentiation from benign prostatic hyperplasia is difficult and the indication for biopsy must be judged individually. Basically, diagnosis is only indicated in those patients, in whom there are therapeutic consequences. The same is true for the use of PSA in follow up after therapy. Further measures should be based on the symptoms of the patient rather than on a laboratory value.     

Histological presence of viable prostatic glands on routine biopsy following cryosurgical ablation of the prostate

PURPOSE: Cryosurgical ablation of the prostate has recently received much attention as a therapeutic alternative for the treatment of localized prostatic adenocarcinoma. Biopsies after treatment reveal a variety of dysplastic changes as well as unaltered prostatic glandular epithelial elements. Prostate specific antigen (PSA) remains undetectable in the majority of men. However, in some PSA increases without demonstrable local recurrence. MATERIALS AND METHODS: A total of 383 patients underwent 447 procedures between June 1990 and January 1994. Of 358 biopsies performed at our institution, 317 (2,075 cores) were available for review. Each core was examined for unaltered prostatic glandular epithelial elements and then scored for the percentage of epithelial glandular involvement according to a scale of: 0-no, 0.5-less than 10%, 1-10 to 25%, 2-25 to 50%, 3-50 to 75% and 4-76 to 100% unaltered prostatic glandular epithelial elements. RESULTS: Of 317 biopsies 158 (49.8%) contained no unaltered prostatic glandular epithelial elements, while 185 (58.3%) and 206 (65%) had 1 core containing 10% and 10 to 25%, respectively, of such elements. Of 262 cases (82.6%) with a mean of 10% unaltered prostatic glandular epithelial elements per core 22 (8.4%) were positive for residual carcinoma. Among 55 cases with more normal epithelium per core 24 (43.6%) were positive for residual carcinoma. Patients with a positive biopsy had a median PSA of 2.02 ng./ml. (average gland/core score 0.54). Median PSA for men with negative biopsies was 0.2 ng./ml. (gland/core score 0.124). CONCLUSIONS: Cryosurgical ablation of the prostate has the ability to ablate prostatic tissue completely, thus rendering it free of glandular elements as determined by biopsy. Increasing PSA can indicate residual glandular elements. Increases in unaltered prostatic glandular epithelial elements with time are not paralleled by increased rates of local disease recurrence. undetectable serum PSA has a low risk of residual unaltered prostatic glandular epithelial elements and localized carcinoma. Results as measured by unaltered prostatic glandular epithelial elements and PSA improve with the surgical experience.     

Diagnosis of prostatic carcinoma: value of random transrectal sonographically guided biopsies

OBJECTIVE: We studied the efficacy of random, transrectal sonographically guided biopsies in the diagnosis of prostatic carcinoma in a high-risk population. SUBJECTS AND METHODS: During a 2-year period, 570 transrectal sonographically guided prostatic biopsies were done because of clinical findings suggestive of prostatic carcinoma. Biopsies of hypoechoic lesions that were suggestive of carcinoma and segmental random biopsies of normal-appearing lobes of the prostate were performed. Transrectal sonographic findings were correlated with results of pathologic examination of the biopsy specimen and with surgical results, when available. RESULTS: Of the 202 patients found to have carcinoma, the carcinoma was detected with directed biopsy in 145 patients (72%). One hundred twenty (71%) of 169 carcinomas were detected with random biopsy when that procedure was performed. Random biopsies were the only method of diagnosing 57 (28%) of the 202 carcinomas, increasing the yield by 39%. CONCLUSION: Yield of carcinoma on transrectal sonographically guided biopsies increases significantly when segmental random biopsies are performed. Transrectal sonographically guided biopsies should include cores through hypoechoic lesions that are suggestive of carcinoma and bilateral segmental random biopsies.     

Prostate carcinoma and long term survival

BACKGROUND: The long term survival of patients with prostate carcinoma is not well understood. The objective of the current study was to investigate the temporal trend of prostate carcinoma mortality in patients who survived > or = 10 years after diagnosis. METHODS: Men with prostate carcinoma diagnosed from 1958 through 1983 in the Stockholm/Gotland region in Sweden and who survived > or = 10 years after the diagnosis were investigated regarding survival beyond 10 years. The expected survival was calculated from an annually selected age and time-matched cohort of men from the general population in the same geographic region. The relative survival was expressed as the annual quotient of the observed survival over the expected survival. RESULTS: The authors identified 1896 patients who had survived > or = 10 years. The relative survival decreased up to approximately 18 years after the diagnosis, whereupon it reached a plateau that was constant up to 30 years after diagnosis. CONCLUSIONS: Men with prostate carcinoma surviving > or = 10 years have an excess mortality compared with age-matched controls. This excess mortality ceases 20 to 23 years after diagnosis and the observed and the expected survival are similar, indicating few, if any, deaths from prostate carcinoma from there on.     

Prostate cancer in African-American men: outcome following radiation therapy with or without adjuvant androgen ablation

It was recently demonstrated that capsaicin desensitization of the tongue can be temporarily reversed during bouts of recurrent or constant stimulation. The present study investigated whether this "stimulus-induced recovery" (SIR) also occurs on skin other than the oral mucosa. Twenty-two subjects received capsaicin treatments on the cheek and on the tongue tip at concentrations (330 and 33 microM) that produced approximately equal sensory irritation on the two sites. Desensitization and SIR occurred on both test sites, although the longer time course of irritation on the face changed the magnitude and form of SIR. There were large individual differences in the extent of desensitization and recovery, and the two phenomena were not correlated across sites, i.e., the capacity for SIR on the tongue was not a good predictor of an individual's capacity for SIR on the face. The results are discussed in terms of possible sources of regional and individual differences, and the implications they may have for the efficacy of topical analgesics that contain capsaicin.     

A comparative assessment of cryosurgical devices: application to prostatic disease

OBJECTIVES: To determine the comparative freezing ability of the Cryotech (CT) and AccuProbe (CMS) cryosurgical systems. METHODS: Four conditions designed to model clinical situations were produced: (1) Single-probe performance in water at 17 degrees C; (2) five-probe performance in water at 17 degrees C; (3) single-probe performance in gel at 22 degrees C; and (4) single-probe performance in bovine liver. Parameters evaluated included temperatures at various time points (rates to and final low temperature), configuration of a freeze zone, and shaft freezing characteristics. In addition, isotherms were measured at predetermined distances from the center of the freeze zone. RESULTS: Both systems provided freezing of various media under operational conditions. In water, the CMS 3-mm probe delivered more rapid freezing temperature rates than the 3-mm CT probe, with a 110 degrees C difference in probe surface temperature. In gel, the CMS probe increased freeze volume fourfold versus a twofold increase for the CT probe. In bovine liver, there was nearly equivalent performance with respect to geometry of the freeze ball. Extrapolation of the CT cooling curve indicated temperature equivalence at 30 minutes. A larger shaft diameter 4.9-mm CT probe produced results similar to the CMS probe in all the tested media. In addition, the freeze configuration of the CMS probe was spherical; the CT configuration was more cylindrical. CMS probe (equivalent diameter) tip temperatures were on average 100 degrees C lower. CONCLUSIONS: Our tests demonstrated differences between the CMS and CT probe. The major differences are in the configuration of the freeze zone and shaft freezing. In equivalent conditions, the CMS 3-mm probe delivered more rapid cooling rates, a more spherical freeze ball, and lower absolute temperatures than the CT 3-mm probe. The larger CT probe produces equivalent freezing temperatures to the CMS probe, albeit with a more spherical shape. However, these in vitro systems may not adequately reflect varied prostate morphology. Further research is under way to determine if these differences affect relative efficacy of cryotherapy of the prostate.     

Hepatocellular carcinoma: power Doppler US with a contrast agent--preliminary results

Tetracaine-induced biphasic structure-functional alterations were investigated in acetylcholinesterase (AChE)-associated membrane vesicles from the electric organ of Torpedo californica. Enzyme assays showed that tetracaine exhibits a biphasic effect on the activity of membrane-bound AChE: increasing it at low concentrations (< 12 mM) and decreasing it at high concentrations (> 12 mM). Fluorescence-polarization experiments demonstrated that tetracaine affects the fluidity of lipid hydrocarbon chains of these membranes in a biphasic manner: increasing it at < 20 mM and decreasing it at > 20 mM. This small molecule also alters the fluidity of the negatively charged lipid head group: increasing it at < 13 mM and remaining essentially at the same level at > 13 mM. The positively charged lipid head group is unaffected. Contrasting effects on AChE activity with changes in membrane fluidity showed that [tetracaine] for AChE activity is comparable to that for the fluidity of the negatively charged lipid head group (12 mM versus 13 mM), but lower than that for a biphasic effect on the fluidity of lipid hydrocarbon chains (12 mM versus 20 mM). Differential scanning microcalorimetry showed that, due to membrane protein-lipid interaction, the lipid-phase transition temperature (tml) is higher for AChE-associated membrane vesicles than for isolated lipids from these membranes. An overall disordering of the membranes by tetracaine, as inferred from the lowering of tml, was also demonstrated. These findings suggested that binding of tetracaine to the lipid polar head group and membrane protein-lipid interaction may contribute to a higher [tetracaine] in inducing a comparable biphasic effect on membrane fluidity. At high [tetracaine], charge interactions between the tetracaine cation and the negatively charged lipid head group may result in a new lipid phase in the membranes, which could reverse the increase in membrane fluidity, resulting in the observed biphasic effect. Although both tetracaine and alcohol are amphiphilic species, they exhibit distinctive structure-functional effects on the membranes, as shown by comparing the results obtained on tetracaine with those previously reported for alcohol. The present observations may have significant physiological implications and may be of importance in understanding the biochemical effects of tetracaine in correlation with its physiological impact.     

Studies on the immunologic behavior of standardized virus-induced rat tumor after cryosurgical and surgical treatment

The authors report on the behavior of a virus-induced tumor in the rat after cryosurgical and surgical treatment and re-implantation of different tumor suspensions. No specific "immune-cryothermic response" could be demonstrated. The principle of the lysis of the re-implantate lies in devitalizing the primary tumor.     

Prostate stroma: physiology

The centrosome must be replicated once, and only once, during each cell cycle. To achieve this somatic cells need to synthesize centrosome proteins, target those centrosome proteins to the parental centrosome, and then assemble the centrosome subunits into a functional organelle. The mechanisms that underlie each of these processes are not known. Studies were performed to investigate whether cellular microtubules are involved in centrosome doubling events. For these experiments, CHO cells were arrested in either hydroxyurea (HU) alone or in HU plus a microtubule inhibitor for 3640 h. The cells then were induced to enter mitosis and the numbers of spindle poles/centrosomes were counted following processing of the cells for immunofluorescence microscopy using anticentrosome antiserum. These studies demonstrated that centrosome replication events occurred in cells arrested with either HU alone or HU and taxol while centrosome replication did not occur in cells treated with HU and either nocodazole or colcemid. Immunoblot analysis determined that centrosome proteins were synthesized in HU/nocodazole-arrested cells and demonstrated that the role of microtubules in the centrosome replication process is not to ensure the synthesis of centrosome subunits. Rather, our results suggest that microtubules may be involved in the transport/targeting of centrosome subunits to the parental centrosome during duplication events. For microtubules to contribute to the transport of centrosome subunits during centrosome doubling, centrosome subunits would need to be able to bind to microtubules. To test this, co-sedimentation studies were performed and it was determined that the centrosome proteins, though overproduced under these conditions, remained soluble in HU/nocodazole-treated cells and co-pelleted with taxol-stabilized microtubules in the presence of GTP and AMP-PNP. Moreover, co-sedimentation of one of the centrosome proteins, PCM-1, with microtubules could be inhibited by pre-incubation of extracts with antibodies against dynactin. Together, these data suggest that during centrosome replication in somatic mammalian cells, PCM-1, and perhaps other centrosome components, are targeted to the centrosome via transport along microtubules by motor complexes that include dynein/dynactin.     

VDDR pacing after His-bundle ablation for paroxysmal atrial fibrillation: a pilot study

His-bundle ablation followed by pacemaker implantation is today a widely accepted therapeutic choice when drug refractoriness of symptomatic AF is evident. The selection of pacing mode in patients suffering from paroxysmal AF is still controversial. Preservation of AV synchrony is an attractive option in patients with paroxysmal AF who undergo His-bundle ablation. The purpose of this study was to examine prospectively the contribution of VDDR pacing for preservation of AV synchrony. After His-bundle ablation a VDDR pacing system was implanted in 17 patients with paroxysmal AF, and all antiarrhythmic drugs were withdrawn. The endpoint of the study was defined as the onset of chronic AF. To document the onset of chronic AF 48-hour Holter recordings were made every 6-8 weeks. After a mean followup of 18.2 (range 14-21) months, VDDR pacing is still operative in 13 patients (77%). Four patients developed chronic AF after a mean follow-up of 6 months. Of several baseline characteristics, only the intraatrial P wave at implantation was significantly smaller in patients developing chronic AF than in patients in whom the VDDR mode is still operative. This pilot study suggests that VDDR pacing is an attractive pacing method for patients with paroxysmal AF after His-bundle ablation. A low intraatrial P wave electrogram at implant was associated with a higher risk for the development of chronic AF.     

Receptive field changes after strokelike cortical ablation: a role for activation dynamics

The reorganization of neural activity that takes place after stroke is of paramount importance in producing functional recovery. Experimental stroke models have suggested that this reorganization may have two phases, but physiology alone cannot fully resolve what causes each phase. Computer modeling suggests that these phases might involve an initial change in dynamics occurring immediately, followed by synaptic plasticity. We combined physiological recording from macaque middle temporal cortex (area MT) with a neural network computer model to examine this first phase of altered cortical function after a small, experimentally induced cortical lesion. Major receptive field (RF) changes seen in the first few days postlesion included both expansion and contraction of receptive fields. Although only expansion could be reproduced in an initial model, addition of inhibitory interneuron loss in a ring around the primary ablation, suggested by immunohistochemical examination, permitted contraction to be replicated as well. We therefore predict that this immunochemical observation reflects an immediate extension of the lesion rather than a late response. Additionally our model successfully predicted a correlation between increased firing rate and RF size. Our model suggests that activation dynamics alone, without anatomic remodeling, can cause the large receptive field changes that allow the rapid behavioral recovery seen after middle temporal lesions.     

Usefulness of CO2 US angiography in treating hepatocellular carcinoma

We evaluated the usefulness of CO2 US angiography in the detectability of and the effectiveness of TAE and/or PEIT for hepatocellular carcinoma (HCC). Twenty-three patients with HCC underwent CO2 angiography during the interventional procedure to treat HCC after examination of CT and conventional US. CO2 US angiography was observed on the US monitor by injecting CO2 microbubbles through a catheter placed in the hepatic artery. Contrast materials for CO2 US angiography were 3 ml of CO2 microbubbles prepared by vigorously mixing 3 ml of normal saline with 3 ml of 20% Intralipid, 3 ml of 20% albumin or 3 ml of the patient's own blood. In all patients, CO2 US angiography revealed equal or superior tumor detectability as compared with CT, conventional US and angiography. For demonstrating the inner structure of HCC, the image of CO2 microbubbles mixed with Intralipid was better than that of CO2 microbubbles mixed with albumin. In 9 of 23 patients, CO2 US angiography depicted nodules that had not been seen in the other images. TAE was performed in 21 patients with HCC who showed hypervascularity. In one patient in whom it was difficult to clearly depict the small lesion of HCC by conventional angiography and US, PEIT was successful under CO2 US angiography. The detectability of HCC was higher in CO2 US angiography than in CT, conventional US or angiography. The distribution of blood supply to HCC was observed easily by CO2 US angiography. In TAE of HCC, CO2 US angiography was useful to determine the dose of embolization materials without having to perform repeated angiography. It was possible to perform PEIT easily for non-detectable tumors without CO2 US angiography. CO2 US angiography was useful to evaluate the stage of HCC and to perform TAE and PEIT.     

Prostate cancer: clinical perspectives

1. When obtaining a screening history for prostate cancer, important risk factors include age, family history, and ethnicity. The digital rectal examination remains the "gold standard" physical examination screening technique. 2. If prostate cancer is detected at an early stage, it is potentially curable. It is incumbent upon occupational health care providers to afford those constituents who fall into a high risk category, or who are > or = 40 years of age, every opportunity for prostate cancer screening. 3. Education is the "sine-qua-non" of complete health care provision for prostate cancer clients. The occupational health care provider can play a pivotal role in allaying a client's fear and misconception of this disease. 4. Providing appropriate assessment and advocacy for clients returning to the workplace following diagnosis and treatment of prostate cancer is crucial.     

Retrospective analysis of 645 simultaneous perineal punch biopsies and transrectal aspiration biopsies for diagnosis of prostatic carcinoma

Four cases of urogenital rhabdomyosarcoma in Nigerian children are reported. One of the patients is alive and well six years after surgical excision of a stage 1 tumour. The remaining three children had more advanced neoplasms and died soon after surgery despite adjuvant therapy with one or more cytotoxic agents. The probable value of combination chemotherapy with vincristine, actinomycin D and cyclophosphamide in this tumour type is discussed.     

Pulmonary vein stenosis after catheter ablation of atrial fibrillation

BACKGROUND: This report describes the complication of pulmonary vein stenosis with resultant severe pulmonary hypertension that developed in 2 patients after successful catheter ablation of chronic atrial fibrillation. METHODS AND RESULTS: Three months after successful catheter ablation of atrial fibrillation, both patients developed progressive dyspnea and pulmonary hypertension. Both were found to have severe stenosis of all 4 pulmonary veins near the junction with the left atrium. Balloon dilation of the stenotic pulmonary veins was performed in these patients, with improvement in dyspnea and pulmonary hypertension. CONCLUSIONS: The complication of pulmonary vein stenosis is potentially life-threatening, and the application of radiofrequency current within the pulmonary veins with standard catheter technology should be avoided. This complication can be treated with balloon dilation, although the long-term course is unknown.