Surgical therapy of locally confined prostate carcinoma

Since prostate specific antigen (PSA) has been established as marker for screening, a dramatic increase of prostatic cancer incidence has been observed over the past years. A further consequence of PSA-measurements lies in the observation that nowadays the majority of newly diagnosed prostatic carcinoma is in a clinically localized stage and therefore amendable to radical prostatectomy in a curative intervention. An important task yet to be solved is to find parameters able to estimate the malignant potential of the tumor preoperatively. Long-term results of radical prostatectomy are explained and the possibilities for reduction of intra- and perioperative complications are discussed.     

Combined iridium 192 afterloading therapy of prostate carcinoma

The goal of radiation therapy is to deliver a high dose to the tumor while preserving normal surrounding tissue. For early-stage prostate cancer, the ultimate conformal irradiation is to place radioactive sources directly into the gland as permanent or temporary seeds. Contemporary prostate brachytherapy incorporates advances in computer analysis, imaging technology, and delivery apparatus, allowing exact and reproducible results. Accurate comparison of brachytherapy to surgery and external beam irradiation requires a randomized study. Comparisons of retrospective studies are fraught with the problems of the heterogeneous nature of early-stage prostate cancer. Pretreatment PSA and grade appear to be more sensitive variables than stage in predicting failure after irradiation. The treatment results based on biopsy are promising for the first two years. Brachytherapy may be considered as a therapeutic option: as monotherapy for early-stage disease and also as a boost following moderate doses of external beam irradiation for locally advanced disease.     

Urethrography and ischial intertuberosity line in radiation therapy planning for prostate carcinoma

We report on our clinical experience with laparoscopic nephrectomy in 35 patients. We have performed a total of 18 transperitoneal laparoscopic nephrectomies (TLN) for benign renal disease. After the introduction of a hydraulic dissecting device, we have since performed 17 retroperitoneal laparoscopic nephrectomies (RLN). These data were compared with those in 19 consecutive open nephrectomies (N). All groups were comparable in terms of indication. The mean operative time for benign disease was 206.5 min for TLN, 211.2 min for RLN and 117 min for N. Analgesic medication requirement per patient was 2 days for TLN, 1 day for RLN and 4 days for N, while the postoperative hospital stay averaged 7 days for TLN, 6 days for RLN and 10 days for N. Our results demonstrate the advantage of a laparoscopic approach over open surgery and also reveal the distinct benefit of a retroperitoneal approach. However, due to the small number of indications this procedure should be restricted to a few urologic centers.     

Hormone therapy in advanced and generalized carcinoma of the prostate]

The prostate grows and functions within a multihormonal environment. It consists of androgens, oestrogens, gonadotrophins, gonadotrophin-releasing hormones and gestagens. Growth factors are produced under the influence of androgen stimulation. We show all possibilities of androgen deprivation of advanced and metastatic prostate cancer.     

Screening for carcinoma of the prostate

In India, cholera is endemic and affects usually the 3 to 5-year-old age group. There have been occasional reports in the neonatal period with Vibrio cholerae O139 Bengal. We report here a case of Vibrio cholerae O1 diarrhea in a 2-day-old, breastfed male, who had been delivered in the hospital and developed severe dehydration.     

Predictors of survival for prostate carcinoma patients treated with salvage radical prostatectomy after radiation therapy

BACKGROUND: Salvage radical prostatectomy is a treatment option for patients with recurrent cancer following radiation therapy. This study was conducted to identify predictors of survival for patients treated with salvage radical prostatectomy. METHODS: The authors studied 86 prostate carcinoma patients who underwent salvage radical prostatectomy for locally persistent or recurrent prostate carcinoma at Mayo Clinic between 1967 and 1996. The mean interval from radiation therapy to biopsy-proven recurrence was 3.7 years (range, 6 months to 17 years). Patient age at surgery ranged from 51 to 78 years (median, 66 years). The mean follow-up after surgery was 5.8 years (range, 1.0-15.2 years). Cox proportional hazards models were used to identify clinical and pathologic factors associated with distant metastasis free survival and cancer specific survival. RESULTS: Actuarial distant metastasis free survival, cancer specific survival, and overall survival were 83%, 91%, and 85% at 5 years and 69%, 64%, and 54% at 10 years, respectively. In multivariate analysis, radical prostatectomy Gleason score and DNA ploidy were independent predictors of distant metastasis free survival and cancer specific survival. CONCLUSIONS: Postirradiation Gleason score and DNA ploidy were highly predictive of the clinical outcomes of patients treated by salvage radical prostatectomy after radiation therapy.     

Early results of a prospective study of hormone therapy for patients with locally advanced prostate carcinoma

BACKGROUND: Locally advanced prostate carcinoma is usually not curable with surgery or radiation therapy. Primary hormone therapy is an alternative therapeutic option, but contemporary prospective studies of the outcomes of such therapy are not available. METHODS: The authors conducted a prospective, hospital-based study of gonadal androgen ablation with deferred antiandrogen therapy in 103 men with prostate carcinoma clinically classified as T3-4NXM0. The median potential follow-up was 51 months (range, 36-74 months), and the median period of observation was 43 months (range, 6-74 months). RESULTS: Each patient experienced regression of the primary tumor, and none experienced significant morbidity from the primary tumor during the study period. The projected 5-year cause specific, metastasis free, PSA disease free (no PSA elevation > 1.0 ng/mL after the beginning of antiandrogen therapy), and all-cause survival rates were 84%, 84%, 68%, and 58%, respectively. CONCLUSIONS: Primary hormone therapy is a reasonable treatment option for locally advanced prostate carcinoma in elderly men or in men with significant comorbid disease who request therapeutic intervention.     

Late rectal bleeding following combined X-ray and proton high dose irradiation for patients with stages T3-T4 prostate carcinoma

PURPOSE: Dose escalation for prostate cancer by external beam irradiation is feasible by a 160 MeV perineal proton beam that reduces the volume of rectum irradiated. We correlated the total doses received to portions of the anterior rectum to study the possible relationship of the volume irradiated to the incidence of late rectal toxicity. METHODS: We have randomized 191 patients with stages T3 and T4 prostatic carcinoma to one of two treatment dose arms. These were: 1) 75.6 Cobalt-Gy-equivalent (CGE), 50.4 Gy delivered by 107-25 MV photons followed by 25.2 CGE delivered perineally by protons (Arm 1) or 2) 67.2 CGE delivered by 10-25 MV photons (Arm 2). RESULTS: With a median follow-up of 3.7 years, post-irradiation rectal bleeding (grades 1 and 2 only, none requiring surgery or hospitalization) from telangiectatic rectal mucosal vessels has occurred in 34% of 99 Arm-1 patients and 16% of 92 Arm-2 patients (p = 0.013). Dose-volume histograms (DVHs) for the anterior rectal wall, the posterior rectal wall and the total rectum in 41 patients treated on Arm 1 were calculated from the three dimensional dose distributions. Rectal bleeding has occurred in 14 or 34% of the 41 DVH-analyzed subset of Arm-1 patients. Both the fractional volume of the anterior rectum and the total dose received by fractional volumes of the anterior rectum significantly correlate with the actuarial probability of bleeding. CONCLUSIONS: Clinicians planning dose escalation to men with localized prostate cancer should approve with caution treatment plans raising more than 40% of the anterior rectum to more than 75 CGE without additional effort to protect the rectal mucosa because this late sequela data indicate that more than half of these men will otherwise have rectal bleeding.     

Prospects for gene therapy in human prostate cancer

Prostate cancer is the most common neoplasm in men and a significant cause of mortality in affected patients. Despite significant advances, current methods of treatment are effective only in the absence of metastatic disease. Gene therapy offers a renewed hope of using the differential characteristics of normal and malignant tissue in constructing treatment strategies. Several clinical trials in prostate cancer gene therapy are currently under way, using immunomodulatory genes, anti-oncogenes, tumor suppressor genes and suicide genes. A continued understanding of the etiological mechanisms involved in the establishment and progression of prostate cancer, along with advances in gene therapy technology, should make gene therapy for prostate cancer therapeutically valuable in the future.     

Dose-volume histogram analysis of patients with hepatocellular carcinoma regarding changes in liver function after proton therapy

Seventy-five patients with hepatocellular carcinoma were treated with proton beams from 1983-1993 at the Proton Medical Research Center, University of Tsukuba. For the purpose of confirming the feasibility of proton therapy for hepatocellular carcinoma, we investigated the influence of proton therapy on liver function and also tried to evaluate the possibility of optimization using dose-volume histogram (DVH) analysis. The results indicated that proton therapy did not cause clinically symptomatic damage in liver function and the only notable change after proton therapy was the transient increase of transminase. DVH analysis showed that this transient increase of transaminase was well correlated to the normal tissue complication probability (NTCP). These results indicate that localized high dose radiation using proton beams is feasible for the treatment of liver cancers and optimization of this treatment may be possible using DVH analysis.     

Clinical application for gene therapy in prostate cancer

We report a patient with peripheral neuropathy caused by cisplatin for the treatment of testicular tumor. Routine studies of nerve conduction and somatosensory evoked potentials demonstrated large myelinated fiber neuropathy suggesting ganglioneuronopathy. We also performed a CO2 laser evoked potential study, and found that small myelinated fibers, which are related to pain sensation, were well preserved in this patient.     

Radiation therapy with neoadjuvant hormonal therapy for prostate cancer confined to pelvis

Neoadjuvant endocrine treatment prior to radical prostatectomy for prostate cancer confined to pelvis has of some value to prevent progression although there are many controversies. In order to improve the prognosis of locally advanced prostate cancer (stage B2 and C), definitive radiotherapy with neoadjuvant endocrine therapy has been investigated. Endocrine therapy reduces the volume of prostate, thus reduces the amount of side effect via reducing the area of irradiated normal tissue. Effect of radiation and that of endocrine therapy to induce apoptosis might be synergistic. The result is favorable although the follow-up period is too short. Further studies are needed to make conclusion.     

Microwave coagulation therapy for hepatocellular carcinoma

BACKGROUND & AIMS: Surgical resection is not always feasible in patients with hepatocellular carcinoma. Microwave coagulation therapy has been used as an alternative to resection, and its efficacy has been evaluated. METHODS: Nineteen patients with unresectable hepatocellular carcinoma underwent microwave coagulation therapy through laparotomy (n = 12), laparoscopy (n = 5), or thoracotomy (n = 2) because of advanced liver cirrhosis and/or intrahepatic metastases. One nodule was treated in 13 patients, tumor size ranged from 5 to 90 mm. Patient outcomes were studied. RESULTS: Microwave coagulation therapy created a reproducible regional necrosis. Fourteen patients underwent potentially curative treatment; the remaining 5 patients underwent palliative treatment (n = 4) or incomplete tumor coagulation (n = 1). Of the 31 nodules treated, 28 underwent complete tumor ablation. Only 2 patients undergoing laparoscopic microwave coagulation therapy developed local recurrence. The coagulated area subsequently shrank. Patients showed rapid recovery without hepatic dysfunction. Thirteen patients, including 2 long-term survivors, are alive either without tumor (n = 10; 14-64 months) or with tumor (n = 3; 17-22 months). Six patients died of hepatocellular carcinoma (n = 4) or liver insufficiency (n = 2). CONCLUSIONS: This preliminary study suggests the efficacy of microwave coagulation therapy, including safety and potential curability, in patients with hepatocellular carcinoma with advanced liver cirrhosis and multifocal or central tumors.     

Late effects of radiation therapy for prostate carcinoma: the patient''s perspective of bladder, bowel and sexual morbidity

Wound repair is characterized by the presence of a fibrin-rich matrix, but the effect of fibrin on re-epithelialization remains unclear. In this study, we determined the effects of different fibrin matrices on cultured human neonatal keratinocytes. Using purified fibrinogen and fibrin gels generated by the enzymatic action of thrombin, batroxobin (it leads to retention of fibrinopeptide B), or Agkistrodon contortrix thrombin-like enzyme (ACTE; it leads to retention of fibrinopeptide A), we determined the effect of each of these matrices on keratinocyte morphology, attachment, spreading, and replication as compared to tissue culture plastic. Morphologically, keratinocytes seeded on fibrin surfaces were more rounded and formed three-dimensional structures. Specific cell attachment, as measured at either 37 degrees C or 4 degrees C, was not altered on the different fibrin substrates (P > .05) but was increased on fibrinogen and factor XIII cross-linked fibrin (P < .01). However, keratinocytes seeded on fibrin, regardless of the presence or absence of fibrinopeptides A or B, showed a marked decrease (up to 71%) in cell numbers by days 5 (P = .0357) and 10 (P = .0114). Keratinocyte spreading was decreased by 78.8% (P = .0006), 80.3% (P = .0001), and 89.2% (P = .0001) on thrombin-, batroxobin-, and ACTE-generated fibrin, respectively, but not on fibrinogen-coated dishes. However, either the addition of fibronectin or cross-linking of fibrin with factor XIII allowed full keratinocyte spreading to occur (P = .0002 and P = .0013, respectively). We conclude that fibrin inhibits keratinocyte spreading in the absence of other matrix or plasma proteins or cross-linking by factor XIII.     

Local interferon therapy for lip carcinoma

In a prospective non-randomized study 21 patients with lower lip squamous cell carcinoma were treated with human natural leukocyte interferon (HNLI). The response rate was measured by a size reduction of more than 25% and was 81%. A complete response rate was considered to be a cure according to histopathological and clinical findings and was 48%. The response rate of six lower lip squamous cell carcinoma cases treated with recombinant interferon alpha 2c was 67% and the complete response rate was 17%. Three patients with basal cell carcinoma of the upper lip were also treated with HNLI. All three patients were cured, as determined by histopathological and clinical findings. These findings indicate that interferon can be a useful alternative therapy for lip carcinoma either with or without surgery.     

Interstitial iodine-125 radiation without adjuvant therapy in the treatment of clinically localized prostate carcinoma

The electrophysiological properties of neurons of the medial septal nucleus and the nucleus of the diagnonal band of Broca (MS/DB) were studied using intracellular methods in urethane-anesthetized rats. Three types of rhythmically bursting neurons were identified in vivo on the basis of their action potential shapes and durations, afterhyperpolarizations (AHPs), membrane characteristics, firing rates and sensitivities to the action of muscarinic antagonist: (1) Cells with short-duration action potentials and no AHPs (2 of 34 rhythmic cells, 6%) had high firing rates and extremely reliable bursts with 6-16 spikes per theta cycle, which were highly resistant to scopolamine action. (2) Cells with short-duration action potentials and short-duration AHPs (8 of 34 rhythmic cells, 24%) also had high firing rates and reliable bursts with 4-13 spikes per theta cycle, phase-locked to the negative peak of the dentate theta wave. Hyperpolarizing current injection revealed a brief membrane time constant, time-dependent membrane rectification and a burst of firing at the break. Depolarizing current steps produced high-frequency repetitive trains of action potentials without spike frequency adaptation. The action potential and membrane and characteristics of this cell type are consistent with those described for GABAergic septal neurons. Many of these neurons retained their theta-bursting pattern in the presence of muscarinic antagonist. (3) Cells with long-duration action potentials and long-duration AHPs (24 of 34 rhythmic cells, 70%) had low firing rates, and usually only 1-3 spikes per theta cycle, locked mainly to the positive peak of the dentate theta rhythm. Hyperpolarizing current injection revealed a long membrane time constant and a break potential; a depolarizing pulse caused a train of action potentials with pronounced spike frequency adaptation. The action potential and membrane properties of this cell type are consistent with those reported for cholinergic septal neurons. The theta-related rhythmicity of this cell type was abolished by muscarinic antagonists. The phasic inhibition of "cholinergic" MS/DB neurons by "GABAergic" MS/DB neurons, followed by a rebound of their firing, is proposed as a mechanism contributing to recruitment of the whole MS/DB neuronal population into the synchronized rhythmic bursting pattern of activity that underlies the occurrence of the hippocampal theta rhythm.     

Usefulness of initial chemoendocrine therapy for advanced prostate cancer

The 5 year cancer specific survival rate of advanced prostate cancer, especially in metastatic cancer is less than 40%. Recently, maximum androgen blockade showed some beneficial effects in cases of minor disease but no additional usefulness in major cases. The treatment modality referred to as initial chemoendocrine, used to treat prostate cancer, seems to be a reasonable method because prostate cancer cells contain heterogeneity. This procedure means that the endocrine treatment is best suited to treat hormone sensitive cells, whereas chemotherapy is more appropriately used as a firstline therapy for hormone insensitive cells. We reported that the initial chemoendocrine method showed superiority in the 5 year cancer specific survival category than in the endocrine therapy analyzing non-randomized trials. From that stage on we reviewed the beneficial point of the treatment, and are now trying randomized control studies.     

Suppression of human prostate carcinoma metastases in severe combined immunodeficient mice by interleukin 2 immunocytokine therapy

Immunocytokines are antibody-cytokine fusion proteins that combine the unique targeting ability of antibodies with the multifunctional activities of cytokines to activate effector cells in the tumor microenvironment. Here, we demonstrate the therapeutic efficacy of a tumor-specific immunocytokine, huKS1/4-IL2, which effectively inhibited growth and dissemination of lung and bone marrow metastases of human prostate carcinoma in severe combined immunodeficient mice. This antitumor effect was specific and highly effective, irrespective of reconstitution of these mice with human lymphokine-activated killer cells. Survival times of mice treated with huKS1/4-IL2 were increased 4-fold as compared with animals treated with a mixture of the corresponding antibody and recombinant human interleukin-2 (rhIL2). A persistent antitumor response after treatment with the huKS1/4-IL2 immunocytokine in B, T, and natural killer cell-deficient severe combined immuodeficient-BEIGE mice, depleted of granulocytes, implies a major role for macrophages in this treatment effect. Our data demonstrate that immunocytokine-directed interleukin-2 therapy to tumor sites is an immunotherapeutic approach with potent effects against disseminated metastases of human prostate carcinoma and suggest that this treatment could be effective in an adjuvant setting for patients with minimal residual disease.